Pain Medicine 2015; 16: 823–829 Wiley Periodicals, Inc.
LETTERS TO THE EDITOR Topical Capsaicin Response as a Phenotypic Measure in Patients with Pain
Dear Editor: Capsaicin, the active component of chili peppers, selectively activates TRPV1 transient receptor potential cation channels, expressed primarily by a subpopulation of afferent C-fibers [1]. Local topical or intradermal application of capsaicin causes burning pain, neurogenic inflammation, hyperalgesia, and a vascular flare response [2]. It yields rather reproducible pain responses in healthy volunteers [3] and is used as an experimental human pain model. More recently, Campbell et al. reported that an increased pain response to capsaicin application is associated with a better treatment response to topical clonidine in painful diabetic neuropathy, presumably linking the capsaicin response to small fiber function [4]. The pain response to capsaicin involves central processing of afferent input and can be modified by placebo manipulation [5], which is activated via descending pain control pathways [6]. Vasodilation, conversely, is mediated by local release of vasoactive mediators such as the calcitonin gene-related peptide (CGRP) and substance P, and does not require cortical processing [7,8]. Hence, for the purpose of functional small-fiber assessment in pain patients, objective measurement of local flare responses may provide a more reliable method. We performed an ad-hoc analysis of data from our recently completed study [9], which may elucidate the difference between assessing objective local flare responses and patient-reported pain following topical capsaicin application. The study was approved by the Regional Research Ethics Committee of Central Denmark (1-10-72-31-12) as part of a research project involving patients with unilateral neuropathic pain in a foot due to peripheral nerve injury [9]. Written informed consent was obtained from each patient prior to participation. All patients underwent quantitative sensory testing (QST) according to the German Research Network on Neuropathic Pain protocol [10]. At baseline, 1 mL of topical 10% capsaicin cream was applied to both (painful and non-painful) dorsal feet (circular 1 cm diameter application). The skin temperature was maintained at 34 C by a feedback lamp. The patients’ pain responses were measured on 0–100 numerical rating scale (NRS) before and every 5 minutes for 30 minutes after capsaicin application. In addition, the local vascular flare response was measured by laser Doppler imaging before and 30 minutes after the application [11].
On a separate day, the patients underwent an ultrasound-guided peripheral nerve block with 2% lidocaine in the affected extremity, resulting in a complete abolition of spontaneous and evoked foot pain [9]. Ninety minutes after the block, while patients still experienced complete pain relief, capsaicin application on both feet was repeated. Lidocaine plasma concentrations were measured at 7 time points up to 120 minutes after the block. Six patients participated in this study. The mean age was 51 (range 18–67) years and 5 patients were male. The neuropathic pain was due to a traumatic (N = 3) or a surgical (N = 3) nerve injury to the peroneal, the tibial, and/or the sural nerves, with median spontaneous pain intensity of 6.5 (range 5–8) on the 0–10 NRS. The QST findings were normal in the non-injured feet, and abnormal in the painful feet, with details described elsewhere [9]. At baseline, the pain intensity at 30 minutes after capsaicin application on the nonpainful foot was 24.2 6 27.6 (on 0–100 NRS), and the local flare response measured by laser Doppler was 249.8 6 138.2 (flux units). After peripheral nerve block has abolished the ongoing pain, capsaicin application on the contralateral (nonpainful) foot resulted in pain intensity of 42.5 6 22.1, a 75.6% increase from baseline (P = 0.050, Student’s t test, normality passed by Shapiro–Wilk test, 0.918) (Figure 1). The area under the pain intensity vs time curve (AUC) over 0–30 minutes was 657.1 (vs 356.2 at baseline; Figure 2). The local capsaicin-evoked flare response measured by laser Doppler flux did not change significantly (232.1 6 98.3 during block vs 249.8 6 138.1 at baseline (P = 0.68), nor did the mean area of flare (8.32 6 2.3 cm2 vs 6.57 6 4.5 cm2 at baseline (P = 0.63). In the ipsilateral (painful) foot, none of the patients experienced any spontaneous or evoked pain response when capsaicin was applied after the nerve block. The local vascular flare response to capsaicin in the ipsilateral foot could not be directly compared to the baseline assessment because of increased skin blood flow and temperature secondary to sympathectomy induced by the nerve block. No temperature changes were observed in the contralateral (unaffected) foot, and plasma lidocaine concentrations 0–120 minutes after the block were low (in all patients less than 1 mcg/mL). Our findings of increased pain response after relief of contralateral pain by a nerve block suggest that the ongoing pain may diminish, or mask, the pain response
823
Letters to the Editor
Figure 1 Individual pain response to topical capsaicin (30 minutes after application) at baseline with ongoing contralateral foot pain, and after nerve block abolished the contralateral pain. NRS = numerical rating scale. associated with topical capsaicin administration, while the local vascular flare response is not affected by ongoing pain. Plausible reasons for this phenomenon may be a distraction due to ongoing pain, or descending pain modulation, activated by the ongoing pain “conditioning.” The order of capsaicin application was not randomized and we cannot exclude the possibility of order effect on pain response intensity; however, other studies have not shown increase in pain response after repeated capsaicin applications [12,13]. It has been shown in animal and human studies that ongoing painful stimuli reduce the level of nociception or pain associated with a different (second) noxious stimulus
[14–16], a phenomenon known as diffuse noxious inhibitory controls or conditioned pain modulation. In a study by Campbell et al. [4], the patients who had high pain response to capsaicin at baseline demonstrated diminished analgesic response to placebo; and as placebo analgesia may be related to activation of the descending pain pathways [6], this may suggest that pain intensity following capsaicin application in patients with ongoing pain is affected by the efficiency of their conditioned pain modulation response. It is important to note that the response to topical capsaicin is not straightforward and is affected by the underlying pain condition and small fiber morphology [11,17,18]. The results of this small study suggest that the pain response to capsaicin represents a complex phenomenon, which may be affected by ongoing pain and needs further investigation. Objective assessment of the local vascular flare response may provide a more reliable outcome measure in this scenario as it does not involve central processing, but the optimal methodology is yet to be determined in larger studies.
SIMON HAROUTOUNIAN, PhD,* LONE NIKOLAJSEN, MD, DMSc,†,‡ NANNA B. FINNERUP, MD, DMSc,† TROELS S. JENSEN, MD, DMSc†,§ *Division of Clinical and Translational Research, Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110; † Danish Pain Research Center, ‡Department of Anesthesiology and §Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
Funding: The study was funded by a grant from the Lundbeck Foundation, Vestagervej 17, 2900 Hellerup, Denmark (R17-A1679). The authors declare no conflicts of interest.
References 1 Caterina MJ, Schumacher MA, Tominaga M, et al. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature 1997;389:816–24. 2 LaMotte RH, Shain CN, Simone DA, Tsai EF. Neurogenic hyperalgesia: Psychophysical studies of underlying mechanisms. J Neurophysiol 1991;66: 190–211.
Figure 2 Area under pain intensity vs time curve 0–30 min after topical 10% capsaicin application at baseline (with ongoing contralateral foot pain), and after nerve block abolished the contralateral pain. NRS = numerical rating scale. 824
3 Gottrup H, Juhl G, Kristensen AD, et al. Chronic oral gabapentin reduces elements of central sensitization in human experimental hyperalgesia. Anesthesiology 2004;101:1400–8. 4 Campbell CM, Kipnes MS, Stouch BC, et al. Randomized control trial of topical clonidine for
Letters to the Editor treatment of painful diabetic neuropathy. Pain 2012; 153:1815–23. 5 Benedetti F, Arduino C, Amanzio M. Somatotopic activation of opioid systems by target-directed expectations of analgesia. J Neurosci 1999;19:3639–48. 6 Eippert F, Bingel U, Schoell ED, et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 2009;63:533–43. 7 Li D, Ren Y, Xu X, et al. Sensitization of primary afferent nociceptors induced by intradermal capsaicin involves the peripheral release of calcitonin gene-related Peptide driven by dorsal root reflexes. J Pain 2008;9:1155–68. 8 Sinclair SR, Kane SA, Van der Schueren BJ, et al. Inhibition of capsaicin-induced increase in dermal blood flow by the oral CGRP receptor antagonist, telcagepant (MK-0974). British J Clin Pharmacol 2010;69:15–22. 9 Haroutounian S, Nikolajsen L, Bendtsen TF, et al. Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy. Pain 2014;155:1272–9. 10 Maier C, Baron R, Tolle TR, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain 2010;150:439–50. 11 Moller AT, Feldt-Rasmussen U, Rasmussen AK, et al. Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin. J Peripher Nerv Syst 2006;11:119–25.
12 Dirks J, Petersen KL, Rowbotham MC, Dahl JB. Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization. Anesthesiology 2002;97:102–7. 13 Hughes A, Macleod A, Growcott J, Thomas I. Assessment of the reproducibility of intradermal administration of capsaicin as a model for inducing human pain. Pain 2002;99:323–31. 14 Le Bars D, Dickenson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications. Pain 1979;6: 305–27. 15 Le Bars D, Dickenson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain 1979;6: 283–304. 16 Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol 2010;23:611–5. 17 Finnerup NB, Pedersen LH, Terkelsen AJ, et al. Reaction to topical capsaicin in spinal cord injury patients with and without central pain. Exp Neurol 2007;205:190–200. 18 Terkelsen AJ, Gierthmuhlen J, Finnerup NB, et al. Bilateral hypersensitivity to capsaicin, thermal, and mechanical stimuli in unilateral complex regional pain syndrome. Anesthesiology 2014;120:1225–36.
Seizures and Transient Neurological Deficits During Epiduroscopy in a Patient with Failed Back Surgery Syndrome Dear Editor: Although epiduroscopy is a minimally invasive technique, reports pertaining to its clinical use and complications are incomplete [1]. We herein present a case study of a patient who experienced seizure and transient neurological deficits during epiduroscopy. A 42-year-old male patient was admitted to an algology clinic with bilateral back and leg pain that was more pronounced in the right leg. According to his medical history, the patient underwent lumbar stabilisation operations in February 2009, but the pain returned following the operations and continued to increase (Figure 1). By the time we saw the patient, his visual analog scale (VAS) pain rating was 9/10. The patient’s straight leg-raising test
performance was normal. There was no neurological deficit, but neuropathic symptoms, including constant burning and tingling, were present especially in the right leg. The patient, whose complaints did not abate despite the use of 300 mg/day pregabalin and 200 mg/day tramadol, did not benefit from physical therapy. Therefore, a fluoroscopy-guided caudal epidural steroid injection was administered. Epiduroscopy was undertaken when the patient’s complaints, which decreased for a month through this procedure, returned to a similar level of severity, with a VAS pain rating of 6/10. The intervention site was cleaned with an iodine-based antiseptic solution in the prone position. Conscious sedation was achieved via 1–2 mg midazolam, 25–50 mg fentanyl, and 30 mg/kg propofol. The intervention site, skin,
825
Letters to the Editor
Figure 1 A: Distribution of the radiopaque substance in epidural space following delivery of the radiopaque substance. The substance was not observed above the L4 level. The filling defect was observed at the L5-S1 level. B: Epiduroscopy cannula was observed above the L4 level. and subcutaneous tissue were anesthetised with 3 mL 2% lidocaine. A disposable endoscopic catheter (EpiduroR , Gouda, The Netherlands) was placed into scopy, Epi-C V the sacral hiatus according to the Seldinger method. Epidurography was performed with 10 mL nonionic contrast material (Iomeron 300, Patheon, Italia SpA) to determine pain-associated pathological structures. As a result of the epidurography, radiopaque material did not exceed L5 levels, and there was no output from foramina. A filling defect was observed in the right side of L5-S1. To get a vision during epiduroscopy, saline was injected at between 0.15 and 0.2 mL/s rates. When volume of saline reached at 100 mL, the following situations were observed; hypertension, decreased oxygen saturation, respiratory arrest, and loss of consciousness during the 10th minute of the procedure, epiduroscopy was immediately terminated. Then mask ventilation was initiated, with the patient in the supine position. A short-term, generalised tonic-clonic seizure was observed. Spontaneous breathing returned and consciousness was regained after approximately 35 minutes. The patient was taken to a postanaesthetic care unit. Complete motor and sensory loss in both of the lower extremities was detected after the patient regained consciousness. It subsequently became clear that the patient’s right lower extremity recovered more quickly than the left lower extremity. Brain magnetic resonance imaging results were judged to be normal, and the patient was returned to the service. The patient was discharged after next-day followup, during which the lower extremity motor power was normal, VAS pain was rated as 2/10, and neuropathic symptoms were reduced. Physiologically normal intracranial pressure is at the level of 5–10 mm Hg at rest. Following extradural injection of
826
10 mL, intracranial pressure increased to between 11 and 63 mm Hg [2]. This increase in pressure occurs within seconds of injection, and may continue to increase pressure for approximately 45 seconds. Increased intracranial pressure has been shown to return to normal levels between 2 minutes, 20 seconds and 5 minutes, 50 seconds [2]. This increase in pressure may be greater in patients with a priori above-average intracranial pressure; 10 mL epidural injection can cause a more serious increase in pressure, up to approximately 300 mm Hg [1]. In the present case, another contributing factor to the seizure was the amount of 0.9% saline infusion used during epiduroscopy. The average amount of Cerebro-spinal fluid (CSF) in humans is 130– 150 mL. When CSF flow is blocked, or the amount of CSF increases, pressure will increase more markedly with the addition of fluid to the system (because the system can be extended only marginally). Therefore, the amounts of steroid, hyaluronic acid, radiopaque substance, and 0.9% saline administered during epiduroscopy should be calculated precisely, and the presence of headache should be assessed intermittently, where headache is an indicator of increased intracranial pressure in patients under sedoanalgesia. If a headache develops, the intervention should be terminated. During the World Initiative on Spinal Endoscopy (WISE) conference, held in Graz, Austria, between March 3, 2006 and March 4, 2006, the amount of liquid used during epiduroscopy was discussed; it was emphasised €tze that this amount should not exceed 200 mL [3]. Schu reported using substantially less liquid, at an average of 85 mL [1]. In a systematic review published in 2013, application of liquid in amounts exceeding 100 mL increased epidural hydrostatic pressure [4]. Gill and Heavner reported that epidural injection should be administered at a low speed of 1 mL/s: a volume of 100 mL/60 min should not
Letters to the Editor be exceeded, and an infusion rate of 0.03 mL/s is appropriate [5]. In the present case, 100 mL saline was infused with 10 mL radiopaque substance. The speed of the liquid infusion, at the onset of the 10 min procedure, may have engendered a rapid increase in epidural pressure. Moreover, the administration of 110 mL liquid in a short period of time increased the pressure in the epidural space, thereby facilitating the opening of pain-causing adhesions. In 2011, Popescu et al. [6] conducted a literature review of the neurological problems observed following epidural injection. A total of 16 neurological cases were reported: paresis or plegia were observed in 10 patients, and seizure was observed in one patient in the form of grand mal epilepsy. The seizure patient received hyperbaric oxygen therapy following the operation [7]. Epiduroscopy is becoming increasingly prevalent. Although it is a safe, minimally invasive technique, the rates of complications resulting from epiduroscopy will increase commensurate with its increasing usage. On the basis of the present case, we believe that the amount of all types of liquids delivered to the spinal canal should be calculated precisely during implementation of the epiduroscopy procedure, and that unnecessary fluid and drug administration should be avoided. Finally, injections of drug or radiopaque substances should be administered slowly and carefully.
SERBU¨LENT GO¨KHAN BEYAZ, MD Anesthesiology and Pain Medicine,
Sakarya University Medical School, Sakarya, Republic of Turkey References €tze G. Epiduroscopy-Spinal Endoscopy, 1st edi1 Schu tion. Germany: Springer; 2008:76–7. 2 Hilt H, Gramm HJ, Link J. Changes in intracranial pressure associated with extradural anesthesia. Br J Anaesth 1986;85:676–80. €tze G, et al. 3 Sandner-Kiesling A, Weber G, Schu Foundation of the World Initiative on Spinal Endoscopy (WISE). Pain Clin 2007;19(2):51–2. 4 Helm S, Hayek SM, Colson J, et al. Spinal endoscopic adhesiolysis in post lumbar surgery syndrome: An update of assessment of the evidence. Pain Physician 2013;16(2 Suppl):SE125–50. 5 Gill JB, Heavner JE. Visual impairment following epidural fluid injections and epiduroscopy: A review. Pain Med 2005;6:367–74. 6 Popescu A, Lai D, Lu A, Gardner K. Stroke following epidural injections—Case report and review of literature. J Neuroimaging 2013;23(1):118–21. 7 McMillan MR, Crumpton C. Cortical blindness and neurologic injury complicating cervical transforaminal injection for cervical radiculopathy. Anesthesiology 2003;99(2):509–11.
Contrast Spread Technique Dear Editor: Loss Of Resistance (LOR) technique (Dogliotti’s principle)1 is well known and widely used, and so is Contrast Spread (CS) technique. This is what Dr. Donald L. Renfrew wrote in his description of how to perform cervical and thoracic epidural steroid injections, with the help of fluoroscopy, more than a decade ago: “When the needle is just behind the spinal canal inject 0.2 to 0.3 mL of nonionic contrast material and confirm position in the posterior soft tissues. Advance the needle very slowly with one hand while pressurizing the syringe (LOR) with the other. When a thin line of CSs along the posterior epidural space, immediately stop advancing the needle!”2 CS technique is intuitively used by many Pain Practitioners to identify epidural space, together with LOR technique, especially with cervical epidurals. However, LOR technique is not as reliable in the upper spine as it is in the lower spine as:
1. The ligamentum flavum is not fused at midline up to 60–70%, thus increasing the risk of false LOR;[1]3 2. The ligamentum flavum is thinner at the cervical spine and it is easier to miss LOR; 3. Epidural space is thinner (1.5–2 mm at C5–C6 and 2.5–3 mm at C7–T1 level at midline and becomes progressively less existent further toward the periphery from the midline);4 [2,3] 4. Fluoroscopic visualization of the needle depth is not always possible due to shoulders obstructing the view with lateral fluoroscopy; 5. The Contralateral Oblique View circumvents the problem with shoulders and allows the practitioner to visualize needle depth when performed properly but cannot identify epidural space entry (LOR and CS techniques can); 6. Finally, the consequences of placing the needle too deep are not as forgiving as with lower spine injections due to the proximity of the spinal cord. (ASA closed claims database 2005–2008: 51 procedure
827
Letters to the Editor related complications and among them 20 (31%) direct trauma to the spinal cord or nerve.)5 [4] One may use CS technique alone to recognize entry into epidural space. In such a case, with the needle close to the epidural space on lateral or contralateral oblique fluoroscopy, one controls needle depth location with incremental injections of a contrast and fluoroscopy. Needle advancement should be slow, no more than 1–2 mm at a time. One follows CS and is able to see qualitative change from soft tissue spread to epidural spread. In case of any doubt, continuous (live) fluoroscopy may be utilized, with the physician monitoring dye spread while injecting a contrast. Low dose or pulsed mode is used with live fluoroscopy to decrease X-ray exposure. Continuous fluoroscopy would clearly differentiate the CS above (soft tissue) or beyond (epidural space) the spinolaminar line. It is easier, however, to combine both techniques: LOR and CS. Utilizing both techniques has the benefit of decreasing the chance of not recognizing epidural space with possible tragic consequences. It also increases the success rate of a procedure as it improves localization of epidural space with an injection. One may argue that the right name for the above described technique would be Contrast Flow technique. When there is a doubt where the medicine goes we often utilize contrast flow under live fluoroscopy. However, spread is a better term for the technique. With cervical epidural injection one should identify the entrance into the epidural space. Injection of the contrast will show the distribution, with dye spreading in soft tissue, or in an epidural space. Flow goes with something that is changing, for example, with the blood stream in the case of intravascular injection, or with spinal fluids in case of subarachnoid injection. And spread goes with something that stays, does not change, like soft tissue or an epidural space. More and more interventional procedures are done with fluoroscopic or ultrasound guidance. CS technique may be taught in residency or fellowship programs with fluoroscopically performed procedures. It is not a substitute for LOR technique, but rather an addition to it that may provide some benefits to Pain Practitioners by improving both the safety and quality of spinal injections.
YAKOV PERPER, MD Private Practice, New York Notes 1. Dogliotti’s principle is a principle in epidural anaesthesia first described by Professor Achille Mario Dogliotti in 1933. It is a method for the identification of the epidural space.Wikipedia, the free encyclopedia. 2. Atlas of Spine Injection. Donald L. Renfrew, M.D. 2004 Elsevier Inc., Tables 2–9 and 2–10, pages 46 and 48. 3. Cervical and high thoracic ligamentum flavum frequently fails to fuse in the midline. 4. There are different opinions on the thickness of cervical epidural space: Midline epidural fat is minimal at C6–7 and there is none at C5–6 and above. Avoiding Catastrophic Complications from Epidural Steroid Injection. The distances from ligamentum flavum to dural sac, representing the depth of the epidural space, averaged 3 mm at C6–C7 level. Skin to cervical epidural space distances as read from magnetic resonance imaging films: consideration of the “hump pad.” Numbers provided for cervical epidural space width is the author’s estimate based on multiple clinical observations. 5. Injury and Liability associated with cervical procedures for chronic pain.
References 1 Lirk P, Kolbitsch C, Putz G, et al. Cervical and high thoracic ligamentum flavum frequently fails to fuse in the midline. Anesthesiology 2003;99(6):1387–90. 2 S. Abram, Q. Hogan. APSF Newsletter springsummer, 2011. 3 Aldrete JA, Mushin AU, Zapata JC, Ghaly R. Skin to cervical epidural space distances as read from magnetic resonance imaging films: consideration of the “hump pad.” J. Clin Anesth 1998;10(4):309–13. 4 Rathmell JP, Michna E, Fitzgibbon DR, et al. Injury and liability associated with cervical procedures for chronic pain. Anesthesiology 2011;114(4):918–26.
Myofascial Trigger Points in Patients with Whiplash-Associated Disorders and Mechanical Neck Pain Dear Editor, By asserting that myofascial trigger points (MTPs) are foci of deep tissue nociception (i.e., muscle damage), Castaldo et al. [1] have assumed the validity of that which still remains to be proved. That others [2,3] have
828
speculated along similar lines does not constitute scientific evidence that supports their argument. Castaldo et al. [1] then claim that MTPs “may perpetuate lowered pain thresholds in uninjured tissues far away from their localization and are one of the most
Letters to the Editor important peripheral pain generators and initiators for central sensitization.” What is the evidence for this assertion and what is the proposed mechanism of such “perpetuation”? The study by Freeman et al., [4] which is cited as evidence, is weakened by its failure to demonstrate that the “trigger points” were foci of tissue damage. Nevertheless, those authors thought it “reasonable” to speculate that these putative entities initially arose as a protective response to injury but they were unable to explain why “such focal pain generators” remained active for so long after the presumed injury had occurred [4]. Nor did they explain how remote pain thresholds could be lowered. According to Castaldo et al. [1], “. . . by treating MTPs, the dysfunctional process of the nervous system may be mitigated leading to clinical improvement.” However in the cited study by Herren-Gerber et al. [5] on which this assertion is based, there is no mention of MTPs. Those researchers only canvassed the possibility of central hypersensitivity in whiplash patients being maintained by ongoing peripheral nociceptive input, which is a far cry from the assertion of Castaldo et al. [1]. We would ask those who still adhere to MTP theory either to explain the pathogenesis of the associated pain or to make it quite clear to their readers that their assertions are still in the realm of speculation. It has yet to be demonstrated that a hypothetical “painful lesion” residing in “myofascial” tissues can be responsible for initiating or maintaining a state of central hypersensitivity, or that “treatment” of such lesions affects the “dysfunctional process of the nervous system” [1].
JOHN QUINTNER, MB BS FFPMANZCA* AND MILTON COHEN, MD FRACP FFPMANZCA† *Arthritis & Osteoporosis WA, Shenton Park, Western Australia, Australia † Pain Medicine and Rheumatology, St Vincent’s Clinical School, UNSW Australia, Sydney NSW, Australia
References 1 Castaldo M, Ge HY, Chlarotto A, Villafane JH, Arendt-Nielsen L. Myofascial trigger points in whiplash-associated disorders and mechanical neck pain. Pain Med 2014;15:842–9. 2 Fricton JR. Myofascial pain and whiplash. Spine: State of the Art Rev 1993;7(3):403–22. 3 Gerwin RD, Dommerholt J. Myofascial trigger points in chronic cervical whiplash syndrome. J Musculoskeletal Pain 1998;6(suppl 2):28. 4 Freeman MD, Nystrom A, Centeno C. Chronic whiplash and central sensitization: an evaluation of the role of myofascial trigger points in pain modulation. J Brachial Plex Periph Nerve Inj 2009;23(4):2. 5 Herren-Gerber R, Weiss S, Arendt-Nielsen L, et al. Modulation of central hypersensitivity by nociceptive input in chronic pain after whiplash injury. Pain Med 2004;5(4):366–76.
Editor’s Response Professors Quintner and colleagues, highly experienced clinical thought leaders, have articulated a referenced critique of the concept of myofascial trigger points as sources of nociception, an argument that they periodically publish in this and other journals. In a Commentary in this Issue of Pain Medicine, Professors Castaldo and ArendtNielsen answer this critique with their own marshalling of the evidence [1]. Their debate raises interesting methodological questions for investigations of pain mechanisms in clinical syndromes. There is no doubt in any clinician’s mind that muscle hurt, that they can be tender to touch and that certain ‘trigger points’ can be very painful when pressed. Of course, a muscle is much more than a collection of muscle cells. It is an organ of nerve fibres, blood vessels, fascia and muscle fibres that together function in their musculoskeletal role as programmed and assigned developmentally and directed by the brain, an organ that itself consists of more than just nerve fibres. Like any other organ that hurts, the complex interaction of peripheral
stimuli and CNS processing accounts for the pain of muscles. Musculoskeletal research centers, like Dr. Arendt-Nielsen’s in Denmark and at the University of Pennsylvania, my institution, will no doubt provide us the answers to the questions raised by these distinguished clinicians and clinical scientists. In the meantime, our patients are fortunate in that we have well-established, evidence-based treatments that help – whether the pain is peripheral in origin, central in origin, or a complex interaction of both - which it usually is.
ROLLIN M. GALLAGHER, MD, MPH Editor-in-Chief REFERENCES 1 Castaldo and Arendt-Nielson reference
829
LETTERS TO THE EDITOR Topical Capsaicin Response as a Phenotypic Measure in Patients with Pain
Dear Editor: Capsaicin, the active component of chili peppers, selectively activates TRPV1 transient receptor potential cation channels, expressed primarily by a subpopulation of afferent C-fibers [1]. Local topical or intradermal application of capsaicin causes burning pain, neurogenic inflammation, hyperalgesia, and a vascular flare response [2]. It yields rather reproducible pain responses in healthy volunteers [3] and is used as an experimental human pain model. More recently, Campbell et al. reported that an increased pain response to capsaicin application is associated with a better treatment response to topical clonidine in painful diabetic neuropathy, presumably linking the capsaicin response to small fiber function [4]. The pain response to capsaicin involves central processing of afferent input and can be modified by placebo manipulation [5], which is activated via descending pain control pathways [6]. Vasodilation, conversely, is mediated by local release of vasoactive mediators such as the calcitonin gene-related peptide (CGRP) and substance P, and does not require cortical processing [7,8]. Hence, for the purpose of functional small-fiber assessment in pain patients, objective measurement of local flare responses may provide a more reliable method. We performed an ad-hoc analysis of data from our recently completed study [9], which may elucidate the difference between assessing objective local flare responses and patient-reported pain following topical capsaicin application. The study was approved by the Regional Research Ethics Committee of Central Denmark (1-10-72-31-12) as part of a research project involving patients with unilateral neuropathic pain in a foot due to peripheral nerve injury [9]. Written informed consent was obtained from each patient prior to participation. All patients underwent quantitative sensory testing (QST) according to the German Research Network on Neuropathic Pain protocol [10]. At baseline, 1 mL of topical 10% capsaicin cream was applied to both (painful and non-painful) dorsal feet (circular 1 cm diameter application). The skin temperature was maintained at 34 C by a feedback lamp. The patients’ pain responses were measured on 0–100 numerical rating scale (NRS) before and every 5 minutes for 30 minutes after capsaicin application. In addition, the local vascular flare response was measured by laser Doppler imaging before and 30 minutes after the application [11].
On a separate day, the patients underwent an ultrasound-guided peripheral nerve block with 2% lidocaine in the affected extremity, resulting in a complete abolition of spontaneous and evoked foot pain [9]. Ninety minutes after the block, while patients still experienced complete pain relief, capsaicin application on both feet was repeated. Lidocaine plasma concentrations were measured at 7 time points up to 120 minutes after the block. Six patients participated in this study. The mean age was 51 (range 18–67) years and 5 patients were male. The neuropathic pain was due to a traumatic (N = 3) or a surgical (N = 3) nerve injury to the peroneal, the tibial, and/or the sural nerves, with median spontaneous pain intensity of 6.5 (range 5–8) on the 0–10 NRS. The QST findings were normal in the non-injured feet, and abnormal in the painful feet, with details described elsewhere [9]. At baseline, the pain intensity at 30 minutes after capsaicin application on the nonpainful foot was 24.2 6 27.6 (on 0–100 NRS), and the local flare response measured by laser Doppler was 249.8 6 138.2 (flux units). After peripheral nerve block has abolished the ongoing pain, capsaicin application on the contralateral (nonpainful) foot resulted in pain intensity of 42.5 6 22.1, a 75.6% increase from baseline (P = 0.050, Student’s t test, normality passed by Shapiro–Wilk test, 0.918) (Figure 1). The area under the pain intensity vs time curve (AUC) over 0–30 minutes was 657.1 (vs 356.2 at baseline; Figure 2). The local capsaicin-evoked flare response measured by laser Doppler flux did not change significantly (232.1 6 98.3 during block vs 249.8 6 138.1 at baseline (P = 0.68), nor did the mean area of flare (8.32 6 2.3 cm2 vs 6.57 6 4.5 cm2 at baseline (P = 0.63). In the ipsilateral (painful) foot, none of the patients experienced any spontaneous or evoked pain response when capsaicin was applied after the nerve block. The local vascular flare response to capsaicin in the ipsilateral foot could not be directly compared to the baseline assessment because of increased skin blood flow and temperature secondary to sympathectomy induced by the nerve block. No temperature changes were observed in the contralateral (unaffected) foot, and plasma lidocaine concentrations 0–120 minutes after the block were low (in all patients less than 1 mcg/mL). Our findings of increased pain response after relief of contralateral pain by a nerve block suggest that the ongoing pain may diminish, or mask, the pain response
823
Letters to the Editor
Figure 1 Individual pain response to topical capsaicin (30 minutes after application) at baseline with ongoing contralateral foot pain, and after nerve block abolished the contralateral pain. NRS = numerical rating scale. associated with topical capsaicin administration, while the local vascular flare response is not affected by ongoing pain. Plausible reasons for this phenomenon may be a distraction due to ongoing pain, or descending pain modulation, activated by the ongoing pain “conditioning.” The order of capsaicin application was not randomized and we cannot exclude the possibility of order effect on pain response intensity; however, other studies have not shown increase in pain response after repeated capsaicin applications [12,13]. It has been shown in animal and human studies that ongoing painful stimuli reduce the level of nociception or pain associated with a different (second) noxious stimulus
[14–16], a phenomenon known as diffuse noxious inhibitory controls or conditioned pain modulation. In a study by Campbell et al. [4], the patients who had high pain response to capsaicin at baseline demonstrated diminished analgesic response to placebo; and as placebo analgesia may be related to activation of the descending pain pathways [6], this may suggest that pain intensity following capsaicin application in patients with ongoing pain is affected by the efficiency of their conditioned pain modulation response. It is important to note that the response to topical capsaicin is not straightforward and is affected by the underlying pain condition and small fiber morphology [11,17,18]. The results of this small study suggest that the pain response to capsaicin represents a complex phenomenon, which may be affected by ongoing pain and needs further investigation. Objective assessment of the local vascular flare response may provide a more reliable outcome measure in this scenario as it does not involve central processing, but the optimal methodology is yet to be determined in larger studies.
SIMON HAROUTOUNIAN, PhD,* LONE NIKOLAJSEN, MD, DMSc,†,‡ NANNA B. FINNERUP, MD, DMSc,† TROELS S. JENSEN, MD, DMSc†,§ *Division of Clinical and Translational Research, Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110; † Danish Pain Research Center, ‡Department of Anesthesiology and §Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
Funding: The study was funded by a grant from the Lundbeck Foundation, Vestagervej 17, 2900 Hellerup, Denmark (R17-A1679). The authors declare no conflicts of interest.
References 1 Caterina MJ, Schumacher MA, Tominaga M, et al. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature 1997;389:816–24. 2 LaMotte RH, Shain CN, Simone DA, Tsai EF. Neurogenic hyperalgesia: Psychophysical studies of underlying mechanisms. J Neurophysiol 1991;66: 190–211.
Figure 2 Area under pain intensity vs time curve 0–30 min after topical 10% capsaicin application at baseline (with ongoing contralateral foot pain), and after nerve block abolished the contralateral pain. NRS = numerical rating scale. 824
3 Gottrup H, Juhl G, Kristensen AD, et al. Chronic oral gabapentin reduces elements of central sensitization in human experimental hyperalgesia. Anesthesiology 2004;101:1400–8. 4 Campbell CM, Kipnes MS, Stouch BC, et al. Randomized control trial of topical clonidine for
Letters to the Editor treatment of painful diabetic neuropathy. Pain 2012; 153:1815–23. 5 Benedetti F, Arduino C, Amanzio M. Somatotopic activation of opioid systems by target-directed expectations of analgesia. J Neurosci 1999;19:3639–48. 6 Eippert F, Bingel U, Schoell ED, et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 2009;63:533–43. 7 Li D, Ren Y, Xu X, et al. Sensitization of primary afferent nociceptors induced by intradermal capsaicin involves the peripheral release of calcitonin gene-related Peptide driven by dorsal root reflexes. J Pain 2008;9:1155–68. 8 Sinclair SR, Kane SA, Van der Schueren BJ, et al. Inhibition of capsaicin-induced increase in dermal blood flow by the oral CGRP receptor antagonist, telcagepant (MK-0974). British J Clin Pharmacol 2010;69:15–22. 9 Haroutounian S, Nikolajsen L, Bendtsen TF, et al. Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy. Pain 2014;155:1272–9. 10 Maier C, Baron R, Tolle TR, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain 2010;150:439–50. 11 Moller AT, Feldt-Rasmussen U, Rasmussen AK, et al. Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin. J Peripher Nerv Syst 2006;11:119–25.
12 Dirks J, Petersen KL, Rowbotham MC, Dahl JB. Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization. Anesthesiology 2002;97:102–7. 13 Hughes A, Macleod A, Growcott J, Thomas I. Assessment of the reproducibility of intradermal administration of capsaicin as a model for inducing human pain. Pain 2002;99:323–31. 14 Le Bars D, Dickenson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications. Pain 1979;6: 305–27. 15 Le Bars D, Dickenson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain 1979;6: 283–304. 16 Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol 2010;23:611–5. 17 Finnerup NB, Pedersen LH, Terkelsen AJ, et al. Reaction to topical capsaicin in spinal cord injury patients with and without central pain. Exp Neurol 2007;205:190–200. 18 Terkelsen AJ, Gierthmuhlen J, Finnerup NB, et al. Bilateral hypersensitivity to capsaicin, thermal, and mechanical stimuli in unilateral complex regional pain syndrome. Anesthesiology 2014;120:1225–36.
Seizures and Transient Neurological Deficits During Epiduroscopy in a Patient with Failed Back Surgery Syndrome Dear Editor: Although epiduroscopy is a minimally invasive technique, reports pertaining to its clinical use and complications are incomplete [1]. We herein present a case study of a patient who experienced seizure and transient neurological deficits during epiduroscopy. A 42-year-old male patient was admitted to an algology clinic with bilateral back and leg pain that was more pronounced in the right leg. According to his medical history, the patient underwent lumbar stabilisation operations in February 2009, but the pain returned following the operations and continued to increase (Figure 1). By the time we saw the patient, his visual analog scale (VAS) pain rating was 9/10. The patient’s straight leg-raising test
performance was normal. There was no neurological deficit, but neuropathic symptoms, including constant burning and tingling, were present especially in the right leg. The patient, whose complaints did not abate despite the use of 300 mg/day pregabalin and 200 mg/day tramadol, did not benefit from physical therapy. Therefore, a fluoroscopy-guided caudal epidural steroid injection was administered. Epiduroscopy was undertaken when the patient’s complaints, which decreased for a month through this procedure, returned to a similar level of severity, with a VAS pain rating of 6/10. The intervention site was cleaned with an iodine-based antiseptic solution in the prone position. Conscious sedation was achieved via 1–2 mg midazolam, 25–50 mg fentanyl, and 30 mg/kg propofol. The intervention site, skin,
825
Letters to the Editor
Figure 1 A: Distribution of the radiopaque substance in epidural space following delivery of the radiopaque substance. The substance was not observed above the L4 level. The filling defect was observed at the L5-S1 level. B: Epiduroscopy cannula was observed above the L4 level. and subcutaneous tissue were anesthetised with 3 mL 2% lidocaine. A disposable endoscopic catheter (EpiduroR , Gouda, The Netherlands) was placed into scopy, Epi-C V the sacral hiatus according to the Seldinger method. Epidurography was performed with 10 mL nonionic contrast material (Iomeron 300, Patheon, Italia SpA) to determine pain-associated pathological structures. As a result of the epidurography, radiopaque material did not exceed L5 levels, and there was no output from foramina. A filling defect was observed in the right side of L5-S1. To get a vision during epiduroscopy, saline was injected at between 0.15 and 0.2 mL/s rates. When volume of saline reached at 100 mL, the following situations were observed; hypertension, decreased oxygen saturation, respiratory arrest, and loss of consciousness during the 10th minute of the procedure, epiduroscopy was immediately terminated. Then mask ventilation was initiated, with the patient in the supine position. A short-term, generalised tonic-clonic seizure was observed. Spontaneous breathing returned and consciousness was regained after approximately 35 minutes. The patient was taken to a postanaesthetic care unit. Complete motor and sensory loss in both of the lower extremities was detected after the patient regained consciousness. It subsequently became clear that the patient’s right lower extremity recovered more quickly than the left lower extremity. Brain magnetic resonance imaging results were judged to be normal, and the patient was returned to the service. The patient was discharged after next-day followup, during which the lower extremity motor power was normal, VAS pain was rated as 2/10, and neuropathic symptoms were reduced. Physiologically normal intracranial pressure is at the level of 5–10 mm Hg at rest. Following extradural injection of
826
10 mL, intracranial pressure increased to between 11 and 63 mm Hg [2]. This increase in pressure occurs within seconds of injection, and may continue to increase pressure for approximately 45 seconds. Increased intracranial pressure has been shown to return to normal levels between 2 minutes, 20 seconds and 5 minutes, 50 seconds [2]. This increase in pressure may be greater in patients with a priori above-average intracranial pressure; 10 mL epidural injection can cause a more serious increase in pressure, up to approximately 300 mm Hg [1]. In the present case, another contributing factor to the seizure was the amount of 0.9% saline infusion used during epiduroscopy. The average amount of Cerebro-spinal fluid (CSF) in humans is 130– 150 mL. When CSF flow is blocked, or the amount of CSF increases, pressure will increase more markedly with the addition of fluid to the system (because the system can be extended only marginally). Therefore, the amounts of steroid, hyaluronic acid, radiopaque substance, and 0.9% saline administered during epiduroscopy should be calculated precisely, and the presence of headache should be assessed intermittently, where headache is an indicator of increased intracranial pressure in patients under sedoanalgesia. If a headache develops, the intervention should be terminated. During the World Initiative on Spinal Endoscopy (WISE) conference, held in Graz, Austria, between March 3, 2006 and March 4, 2006, the amount of liquid used during epiduroscopy was discussed; it was emphasised €tze that this amount should not exceed 200 mL [3]. Schu reported using substantially less liquid, at an average of 85 mL [1]. In a systematic review published in 2013, application of liquid in amounts exceeding 100 mL increased epidural hydrostatic pressure [4]. Gill and Heavner reported that epidural injection should be administered at a low speed of 1 mL/s: a volume of 100 mL/60 min should not
Letters to the Editor be exceeded, and an infusion rate of 0.03 mL/s is appropriate [5]. In the present case, 100 mL saline was infused with 10 mL radiopaque substance. The speed of the liquid infusion, at the onset of the 10 min procedure, may have engendered a rapid increase in epidural pressure. Moreover, the administration of 110 mL liquid in a short period of time increased the pressure in the epidural space, thereby facilitating the opening of pain-causing adhesions. In 2011, Popescu et al. [6] conducted a literature review of the neurological problems observed following epidural injection. A total of 16 neurological cases were reported: paresis or plegia were observed in 10 patients, and seizure was observed in one patient in the form of grand mal epilepsy. The seizure patient received hyperbaric oxygen therapy following the operation [7]. Epiduroscopy is becoming increasingly prevalent. Although it is a safe, minimally invasive technique, the rates of complications resulting from epiduroscopy will increase commensurate with its increasing usage. On the basis of the present case, we believe that the amount of all types of liquids delivered to the spinal canal should be calculated precisely during implementation of the epiduroscopy procedure, and that unnecessary fluid and drug administration should be avoided. Finally, injections of drug or radiopaque substances should be administered slowly and carefully.
SERBU¨LENT GO¨KHAN BEYAZ, MD Anesthesiology and Pain Medicine,
Sakarya University Medical School, Sakarya, Republic of Turkey References €tze G. Epiduroscopy-Spinal Endoscopy, 1st edi1 Schu tion. Germany: Springer; 2008:76–7. 2 Hilt H, Gramm HJ, Link J. Changes in intracranial pressure associated with extradural anesthesia. Br J Anaesth 1986;85:676–80. €tze G, et al. 3 Sandner-Kiesling A, Weber G, Schu Foundation of the World Initiative on Spinal Endoscopy (WISE). Pain Clin 2007;19(2):51–2. 4 Helm S, Hayek SM, Colson J, et al. Spinal endoscopic adhesiolysis in post lumbar surgery syndrome: An update of assessment of the evidence. Pain Physician 2013;16(2 Suppl):SE125–50. 5 Gill JB, Heavner JE. Visual impairment following epidural fluid injections and epiduroscopy: A review. Pain Med 2005;6:367–74. 6 Popescu A, Lai D, Lu A, Gardner K. Stroke following epidural injections—Case report and review of literature. J Neuroimaging 2013;23(1):118–21. 7 McMillan MR, Crumpton C. Cortical blindness and neurologic injury complicating cervical transforaminal injection for cervical radiculopathy. Anesthesiology 2003;99(2):509–11.
Contrast Spread Technique Dear Editor: Loss Of Resistance (LOR) technique (Dogliotti’s principle)1 is well known and widely used, and so is Contrast Spread (CS) technique. This is what Dr. Donald L. Renfrew wrote in his description of how to perform cervical and thoracic epidural steroid injections, with the help of fluoroscopy, more than a decade ago: “When the needle is just behind the spinal canal inject 0.2 to 0.3 mL of nonionic contrast material and confirm position in the posterior soft tissues. Advance the needle very slowly with one hand while pressurizing the syringe (LOR) with the other. When a thin line of CSs along the posterior epidural space, immediately stop advancing the needle!”2 CS technique is intuitively used by many Pain Practitioners to identify epidural space, together with LOR technique, especially with cervical epidurals. However, LOR technique is not as reliable in the upper spine as it is in the lower spine as:
1. The ligamentum flavum is not fused at midline up to 60–70%, thus increasing the risk of false LOR;[1]3 2. The ligamentum flavum is thinner at the cervical spine and it is easier to miss LOR; 3. Epidural space is thinner (1.5–2 mm at C5–C6 and 2.5–3 mm at C7–T1 level at midline and becomes progressively less existent further toward the periphery from the midline);4 [2,3] 4. Fluoroscopic visualization of the needle depth is not always possible due to shoulders obstructing the view with lateral fluoroscopy; 5. The Contralateral Oblique View circumvents the problem with shoulders and allows the practitioner to visualize needle depth when performed properly but cannot identify epidural space entry (LOR and CS techniques can); 6. Finally, the consequences of placing the needle too deep are not as forgiving as with lower spine injections due to the proximity of the spinal cord. (ASA closed claims database 2005–2008: 51 procedure
827
Letters to the Editor related complications and among them 20 (31%) direct trauma to the spinal cord or nerve.)5 [4] One may use CS technique alone to recognize entry into epidural space. In such a case, with the needle close to the epidural space on lateral or contralateral oblique fluoroscopy, one controls needle depth location with incremental injections of a contrast and fluoroscopy. Needle advancement should be slow, no more than 1–2 mm at a time. One follows CS and is able to see qualitative change from soft tissue spread to epidural spread. In case of any doubt, continuous (live) fluoroscopy may be utilized, with the physician monitoring dye spread while injecting a contrast. Low dose or pulsed mode is used with live fluoroscopy to decrease X-ray exposure. Continuous fluoroscopy would clearly differentiate the CS above (soft tissue) or beyond (epidural space) the spinolaminar line. It is easier, however, to combine both techniques: LOR and CS. Utilizing both techniques has the benefit of decreasing the chance of not recognizing epidural space with possible tragic consequences. It also increases the success rate of a procedure as it improves localization of epidural space with an injection. One may argue that the right name for the above described technique would be Contrast Flow technique. When there is a doubt where the medicine goes we often utilize contrast flow under live fluoroscopy. However, spread is a better term for the technique. With cervical epidural injection one should identify the entrance into the epidural space. Injection of the contrast will show the distribution, with dye spreading in soft tissue, or in an epidural space. Flow goes with something that is changing, for example, with the blood stream in the case of intravascular injection, or with spinal fluids in case of subarachnoid injection. And spread goes with something that stays, does not change, like soft tissue or an epidural space. More and more interventional procedures are done with fluoroscopic or ultrasound guidance. CS technique may be taught in residency or fellowship programs with fluoroscopically performed procedures. It is not a substitute for LOR technique, but rather an addition to it that may provide some benefits to Pain Practitioners by improving both the safety and quality of spinal injections.
YAKOV PERPER, MD Private Practice, New York Notes 1. Dogliotti’s principle is a principle in epidural anaesthesia first described by Professor Achille Mario Dogliotti in 1933. It is a method for the identification of the epidural space.Wikipedia, the free encyclopedia. 2. Atlas of Spine Injection. Donald L. Renfrew, M.D. 2004 Elsevier Inc., Tables 2–9 and 2–10, pages 46 and 48. 3. Cervical and high thoracic ligamentum flavum frequently fails to fuse in the midline. 4. There are different opinions on the thickness of cervical epidural space: Midline epidural fat is minimal at C6–7 and there is none at C5–6 and above. Avoiding Catastrophic Complications from Epidural Steroid Injection. The distances from ligamentum flavum to dural sac, representing the depth of the epidural space, averaged 3 mm at C6–C7 level. Skin to cervical epidural space distances as read from magnetic resonance imaging films: consideration of the “hump pad.” Numbers provided for cervical epidural space width is the author’s estimate based on multiple clinical observations. 5. Injury and Liability associated with cervical procedures for chronic pain.
References 1 Lirk P, Kolbitsch C, Putz G, et al. Cervical and high thoracic ligamentum flavum frequently fails to fuse in the midline. Anesthesiology 2003;99(6):1387–90. 2 S. Abram, Q. Hogan. APSF Newsletter springsummer, 2011. 3 Aldrete JA, Mushin AU, Zapata JC, Ghaly R. Skin to cervical epidural space distances as read from magnetic resonance imaging films: consideration of the “hump pad.” J. Clin Anesth 1998;10(4):309–13. 4 Rathmell JP, Michna E, Fitzgibbon DR, et al. Injury and liability associated with cervical procedures for chronic pain. Anesthesiology 2011;114(4):918–26.
Myofascial Trigger Points in Patients with Whiplash-Associated Disorders and Mechanical Neck Pain Dear Editor, By asserting that myofascial trigger points (MTPs) are foci of deep tissue nociception (i.e., muscle damage), Castaldo et al. [1] have assumed the validity of that which still remains to be proved. That others [2,3] have
828
speculated along similar lines does not constitute scientific evidence that supports their argument. Castaldo et al. [1] then claim that MTPs “may perpetuate lowered pain thresholds in uninjured tissues far away from their localization and are one of the most
Letters to the Editor important peripheral pain generators and initiators for central sensitization.” What is the evidence for this assertion and what is the proposed mechanism of such “perpetuation”? The study by Freeman et al., [4] which is cited as evidence, is weakened by its failure to demonstrate that the “trigger points” were foci of tissue damage. Nevertheless, those authors thought it “reasonable” to speculate that these putative entities initially arose as a protective response to injury but they were unable to explain why “such focal pain generators” remained active for so long after the presumed injury had occurred [4]. Nor did they explain how remote pain thresholds could be lowered. According to Castaldo et al. [1], “. . . by treating MTPs, the dysfunctional process of the nervous system may be mitigated leading to clinical improvement.” However in the cited study by Herren-Gerber et al. [5] on which this assertion is based, there is no mention of MTPs. Those researchers only canvassed the possibility of central hypersensitivity in whiplash patients being maintained by ongoing peripheral nociceptive input, which is a far cry from the assertion of Castaldo et al. [1]. We would ask those who still adhere to MTP theory either to explain the pathogenesis of the associated pain or to make it quite clear to their readers that their assertions are still in the realm of speculation. It has yet to be demonstrated that a hypothetical “painful lesion” residing in “myofascial” tissues can be responsible for initiating or maintaining a state of central hypersensitivity, or that “treatment” of such lesions affects the “dysfunctional process of the nervous system” [1].
JOHN QUINTNER, MB BS FFPMANZCA* AND MILTON COHEN, MD FRACP FFPMANZCA† *Arthritis & Osteoporosis WA, Shenton Park, Western Australia, Australia † Pain Medicine and Rheumatology, St Vincent’s Clinical School, UNSW Australia, Sydney NSW, Australia
References 1 Castaldo M, Ge HY, Chlarotto A, Villafane JH, Arendt-Nielsen L. Myofascial trigger points in whiplash-associated disorders and mechanical neck pain. Pain Med 2014;15:842–9. 2 Fricton JR. Myofascial pain and whiplash. Spine: State of the Art Rev 1993;7(3):403–22. 3 Gerwin RD, Dommerholt J. Myofascial trigger points in chronic cervical whiplash syndrome. J Musculoskeletal Pain 1998;6(suppl 2):28. 4 Freeman MD, Nystrom A, Centeno C. Chronic whiplash and central sensitization: an evaluation of the role of myofascial trigger points in pain modulation. J Brachial Plex Periph Nerve Inj 2009;23(4):2. 5 Herren-Gerber R, Weiss S, Arendt-Nielsen L, et al. Modulation of central hypersensitivity by nociceptive input in chronic pain after whiplash injury. Pain Med 2004;5(4):366–76.
Editor’s Response Professors Quintner and colleagues, highly experienced clinical thought leaders, have articulated a referenced critique of the concept of myofascial trigger points as sources of nociception, an argument that they periodically publish in this and other journals. In a Commentary in this Issue of Pain Medicine, Professors Castaldo and ArendtNielsen answer this critique with their own marshalling of the evidence [1]. Their debate raises interesting methodological questions for investigations of pain mechanisms in clinical syndromes. There is no doubt in any clinician’s mind that muscle hurt, that they can be tender to touch and that certain ‘trigger points’ can be very painful when pressed. Of course, a muscle is much more than a collection of muscle cells. It is an organ of nerve fibres, blood vessels, fascia and muscle fibres that together function in their musculoskeletal role as programmed and assigned developmentally and directed by the brain, an organ that itself consists of more than just nerve fibres. Like any other organ that hurts, the complex interaction of peripheral
stimuli and CNS processing accounts for the pain of muscles. Musculoskeletal research centers, like Dr. Arendt-Nielsen’s in Denmark and at the University of Pennsylvania, my institution, will no doubt provide us the answers to the questions raised by these distinguished clinicians and clinical scientists. In the meantime, our patients are fortunate in that we have well-established, evidence-based treatments that help – whether the pain is peripheral in origin, central in origin, or a complex interaction of both - which it usually is.
ROLLIN M. GALLAGHER, MD, MPH Editor-in-Chief REFERENCES 1 Castaldo and Arendt-Nielson reference
829
