Clinical Neurology and Neurosurgery 127 (2014) 101–105
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Peripheral field stimulation for thoracic post herpetic neuropathic pain Zion Zibly 1 , Mayur Sharma 1 , Andrew Shaw, Milind Deogaonkar ∗ Department of Neurosurgery, Center of Neuromodulation, Wexner Medical Center, The Ohio State University, Columbus, USA
a r t i c l e
i n f o
Article history: Received 11 June 2014 Received in revised form 3 September 2014 Accepted 12 October 2014 Keywords: Peripheral field stimulation Neuromodulation Thoracic Post-herpetic Neuropathic pain
a b s t r a c t Objective: Post herpetic neuralgia is a chronic, debilitating pain with very few management options and is often refractory to treatment. We present our experience with a series of 4 patients who underwent subcutaneous peripheral field stimulation for treatment of thoracic post herpetic neuropathic pain. Methods: Four patients with intractable thoracic post herpetic neuropathic pain were operated after maximum medical treatment and a neuropsychological evaluation. Multiple percutaneous electrodes were placed in the subcutaneous plane in the region of pain for a 7-day trial. Following a successful trial (more than 50% reduction of pain), the electrodes were then internalized and attached to a pulse generator. Visual analog scores (VAS) were studied during the preoperative, immediate postoperative and last follow-up visits. Long-term treatment results were determined by retrospective review of medical records. Average follow-up period was 28.2 months. Results: All 4 patients showed persistent improvement in their VAS pain scores with an average improvement of more than 75%. There were no treatment failures and no complication requiring re-operation was reported. Conclusion: Peripheral field stimulation for the treatment of post herpetic neuropathic pain is a safe and effective method for pain relief for an extremely complex problem with very few solutions. Patient selection and proper lead placement is most important for the success of treatment. © 2014 Published by Elsevier B.V.
1. Introduction Post herpetic neuralgic (PHN) pain is a prevalent chronic neuropathic pain. It follows the eruption of varicella herpes zoster virus (VZV, chickenpox). It is estimated that 1 million new cases of VZV are reported annually in the United States alone [1]. Of those approximately 20–30% will develop PHN. The disorder is defined by three distinctive groups. Acute herpetic neuralgia that develops within 30 days of rash onset, sub-acute herpetic neuralgia which develops within 30–120 days after rash onset and post herpetic neuralgia which is defined as pain lasting at least 120 days following rash onset [2,3]. PHN leads to significant morbidity, diminished
Abbreviations: PFS, peripheral field stimulation; PHN, post-herpetic neuralgia; VZV, Varicella zoster virus; VAS, visual analog scale; IPG, implantable pulse generator. ∗ Corresponding author at: Center of Neuromodulation, Wexner Medical center, The Ohio State University, 480 Medical Center Drive Columbus, OH 43210, USA. Tel.: +1 614 366 2420; fax: +1 614 366 8779. E-mail address: [email protected] (M. Deogaonkar). 1 These authors contributed equally. http://dx.doi.org/10.1016/j.clineuro.2014.10.009 0303-8467/© 2014 Published by Elsevier B.V.
quality of life and decreased productivity. Typically PHN presents as variable pain (moderate to severe) and described by patients as burning, stabbing, shooting or gnawing. The involved area usually presents a dermatome belt of one or more nerves and there might be skin color changes or scarring [4,5]. Mostly, physical examination reveals tactile allodynia [6]. Management of PHN consists of Tricyclic antidepressants, anticonvulsants, morphine and lidocaine patches. These treatment offer moderate success and some patients will continue to have chronic PHN pain [7]. Combination therapy of topical capsaicin and aspirin creams was also reported as well as intrathecal methylprednisolone [7,8]. Various non-invasive [transcutaneous electrical nerve stimulation (TENS), repetitive Transcranial Magnetic Stimulation (rTMS), and transcranial direct current stimulation (tDCS)] and invasive [peripheral nerve stimulation (PNS), peripheral field stimulation (PFS), nerve root stimulation (NRS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and motor cortex stimulation (MCS)] neurostimulation techniques have been explored in patients with medical refractory pain syndromes with varied success[9–11]. Due to the success of peripheral field stimulation (PFS) in the treatment of variety of neuropathic pain, there have been few reports of treating PHN via PFS [12–16].
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Here we report our experience with a series of 4 cases of refractory thoracic PHN that were successfully treated with PFS. 2. Methods 2.1. Patient selection Following approval from our institutional review board, a retrospective review of 4 patients with thoracic PHN who were treated with PFS between 2010 and 2013 was done. All patients were referred by pain management specialists in our institution and one by another facility. All the patients were diagnosed to have classical symptoms of PHN and were non responsive to multiple pharmacological medical therapy and other interventions such as nerve blocks. Prior to surgical intervention neuropsychologist confirmed patients to be free of narcotic overuse and psychiatric comorbidities. The pain was assessed using a visual analog scale (VAS) which is a reliable non-verbal measurement scale (10 cm scale, with “0” being considered as “no pain” and “10” being “worst imaginable pain”) commonly used to assess pain and disability [17,18] The neuropsychological evaluation was performed using battery for health improvement inventory (BHI-2), the pain Catastrophizing Scale (PCS) and various pain management instruments as part of comprehensive evaluation. In addition, scores on measures of depression, anxiety and hostility as well as alcohol or illicit drug dependence were evaluated in all patients prior to implantation. The average age of the patient at PFS implantation surgery was 47.5 ± 8.75 years. Half of the patients were males. All patients underwent a PFS trial done by our team. The 7-day trial period was used in order to confirm at least 50% reduction in the pain VAS score. Following successful PFS trial the patients underwent implantation of permanent lead stimulator and a pulse generator.
Fig. 1. Two octode PFS leads bracketing the area of PHN pain on the right anterior thoracic wall.
2.2. Surgical technique As described in patient selection, surgery is done as a two stage procedure. For the trial procedure, the patient is awake. Area of pain and allodynia is marked before induction of local anesthesia and sedation. The surgical site is prepped and draped. A small skin puncture is made with a Tuohy needle. ON-Q® tunneler (I-Flow, Lake Forest, CA) that is molded to match the curvature of the thoracic region is introduced into the subcutaneous place by virtue of its flexibility and atraumatic tip. Four or eight contact cylindrical leads [Quad, Octad, Quad Plus, or Quad Compact (Medtronic, Inc, Minneapolis, MN)] are placed in the region of pain that is demarcated preoperatively in the same plane. We preferentially use an ON-Q tunneler (I-Flow, Lake Forest, CA) for the placement of cylindrical leads. The direction of tunneling and placing the lead is chosen to be either along the border of pain if there is significant allodynia or underlying the area of pain if allodynia is minimal. Leads are then anchored with a skin stitch. Trial stimulation with externalized battery is then carried out for 7 days. In case of successful trial (more than 50% improvement in pain), permanent implant is done along with an implantable pulse generator (IPG) placement (Activa SC or Activa RC; Medtronic, Inc, Minneapolis, MN). The permanent implant is similar to trial lead placement, except the leads are placed using small skin incisions and are anchored subcutaneously and then tunneled to the IPG site (Figs. 1–4). A rechargeable IPG is placed in an IPG pocket either in infraclavicular region or over abdominal wall or over the hip.
Fig. 2. Three PFS leads (2 quads and 1 octode) below the area of PHN pain on the left anterior and posterior thoracic wall and implantable pulse generator in the left subclavicular region.
2.3. Pain assessment, functional status and data collection Following implantation of the PFS, patients were scheduled for an immediate post-operative visit at 10 days and then outpatient
Fig. 3. Four quad PFS leads bracketing the area of PHN pain on the left anterior and posterior thoracic wall.
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at the last follow up was 2.5 ± 1.3. The average reduction in VAS score was 6.5 ± 1 or 72%. The highest reduction in VAS score was 8 (88%) whereas the lowest was 6 (67%). Patients reported impressive improvement in their quality of life, social activity, return to work and activities as compared to pre PHN pain. Case 4 had already retired. All patients reported more than 80% area coverage by stimulation.
3.3. Adverse events During the follow up period there were no reports of either major or minor complications that required reoperation.
4. Discussion 4.1. PHN: the scope of problem
Fig. 4. Two octode PFS leads below the area of PHN pain on the anterior thoracic wall and implantable pulse generator in the buttock region.
clinic visits as needed for programming. During these visits programming of the stimulation setting was done as needed and VAS recorded. Functional status was assessed by patients’ report of returning to work, social activity and their return to daily activities as prior to occurrence of the PHN. 3. Results 3.1. Patients demographics The demographic characteristic of patients (n = 4) with postherpetic neuralgia who underwent PFS implantation surgery is mentioned in Table 1. Prior history of VZV and PHN was well documented in all four patients. The location of the PHN in all 4 patients was along the thoracic dermatome distribution. Duration of PHN was 3–8 years. Two patients had allodynia and two had hyperalgesia with minimal allodynia that required placement of leads below the area of pain. None of the patients in our series had hypoesthesia or anesthesia in the region of pain (anesthesia dolorosa/deafferentiation pain). Average period of follow up was 28.25 ± 11.6 months (min 5 months, max 36 months). 3.2. VAS changes Average VAS score at baseline was 9, with lowest VAS score of 7 and highest VAS score of 10. Average immediate post op VAS was 2 indicating a reduction of 78% (Fig. 5). The average VAS score
Post herpetic neuralgia (PHN) is one of the most challenging chronic neuropathic pain syndromes. It is also the third most common cause of neuropathic pain in the United States [1,19]. PHN is defined as pain persisting for more than 4 months after the onset of herpes zoster rash [12,20]. PHN pain also seems to be more severe in patients who present with sensory disturbances, allodynia and hyperalgesia, when compared to other types of neuropathic pain [21]. Patients with PHN presents with constant burning, throbbing, arching type of pain or intermittent sharp, shooting pain with tactile allodynia [12,22]. The reactivation of dormant varicella zoster virus causes inflammation of the sensory ganglia and peripheral nerves and thereby inducing abnormal sensitization and hyperexcibility [4]. This reactivation generally occurs in elderly immunodeficient patients or following stressful episodes [22,23]. There are three distinct pathophysiological mechanisms which can explain the symptomatology associated with PHN, first constant firing from abnormally hyperactive but anatomically intact primary afferent nociceptors resulting in central hypersensitization with allodynia [4,12,22,24,25]; Second, loss of C-nociceptors and fibers that initiate central sprouting of A-beta fibers, which make contact with the nociceptors leading to hyperalgesia and allodynia [4,12,22,26]; third, loss of both large and small diameter fibers generates spontaneous activity in deafferented central neurons and produce constant pain in the region of profound sensory deficits without allodynia (anesthesia dolorosa) [4,12,22]. Due to the interplay of these mechanisms in the generation of PHN, a single treatment modality might not be effective and therefore in the majority of patients multidrug regimens are required to achieve pain relief of >50%. Various pharmacological measures such as tricyclic antidepressants, anticonvulsants (pregablin and gabapentin), morphine sulphate, tramadol, controlled release oxycodone, lidocaine patches, topical capsaicin, continues subcutaneous ketamine infusion and intrathecal methylprednisolone have been proved to be efficacious in controlling the pain associated with PHN [7,8,27]. Spinal cord stimulation (SCS) was also described and used for the treatment of PHN. Harke et al. described a series of 28 patients who were treated with SCS for PHN and reported pain relief in 82% of the studied group [22]. However despite the availability of these pharmacological and surgical measures, a significant number of patients do not achieve adequate pain relief. The postulated mechanisms of the failure of pharmacotherapy in PHN are potential ineffectiveness, intolerability due to significant side effects, tolerance and inability to administer optimal dosage especially in elderly patients with significant cardiac and CNS comorbidities [22,28].
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Table 1 Demographic characteristic of patients (n = 4) with post-herpetic neuralgia who underwent PFS implantation surgery. Patient
Age in yrs./Gender
History of VZV and PHN
Location of PHN
Preoperative VAS score
Immediate Postoperative VAS score
Postoperative VAS score at last follow up
Adverse events
Patient 1
43/Female
Yes
10/10
2/10
2/10
None
Patient 2
38/Male
Yes
9/10
3/10
3/10
None
Patient 3
44/Male
Yes
10/10
4/10
4/10
None
Patient 4
65/Female
Yes
Thoracic (T6-12). Thoracic (T10-12) Thoracic (T9-12). Thoracic (T10-12)
7/10
0/10
1/10
None
PFS: peripheral field stimulation; VZV: varicella zoster virus; PHN: post-herpetic neuralgia; VAS: visual analog scale (min = 0, no pain; max = 10, worst pain).
Fig. 5. Preoperative and postoperative (following PFS implantation surgery) pain intensity on visual analog scale (VAS) in four patients with PHN.
4.2. Role of PFS in treatment of PHN The first description of electric stimulation of the peripheral nerves by implanting electrodes for the relieve of chronic cutaneous pain in four patients was reported by Wall et al. in 1967 [29]. PFS has been used for the treatment of a variety of chronic neuropathic pain syndromes such as cervicogenic headaches, migraines [16,30–34], atypical trigeminal neuralgia or facial pain [35], chronic shoulder pain [36], diabetic neuropathic and chronic abdominal pain [12,37,38]. As regards PFS for the treatment of cutaneous PHN, there have been only case reports. Surjya et al. reported successful treatment in a patient who developed painful supra orbital PHN following chemotherapy [12]. In their study, the authors reported 100% reduction in pain intensity during an 8-week follow up. They also reported that the patient was free of all pain management following implantation of the PFS. Kouroukli et al. reported two cases of thoracic PHN treated with PFS who had dramatic reduction in pain [39]. In a randomized trial reported by Guiseppe et al., patients who presented with PHN were treated with Scrambler therapy, which is a noninvasive superficial electric stimulation [40,41]. In this study, the group of patients treated with the electric stimulation showed much higher reduction of pain. 4.3. Our experience Our series included four patients who presented with thoracic PHN. To the best of knowledge this is the largest number of patients treated with PFS. The location of the pain was thoracic in all four. Average immediate post op VAS reduction was 78% (Fig. 5). The average VAS score at the last follow up was 72%. The highest reduction in VAS score was 88% whereas the lowest was 70%. Patients reported improvement in their quality of life, social activity, return
to work and activities. This study presents the longest follow up period for PNFS for the treatment of PHN. The advantages of PFS are minimally invasive procedure, focused stimulation and no spillover of stimulation to other areas. With spinal cord stimulation it is very difficult to cover the axial narrow areas of pain as in PHN and there is a large unwanted and often annoying spillover of stimulation to other areas of trunk or extremities. 4.4. Patient selection and lead location Patient selection and lead location planning are the key factors for good clinical outcome. The exclusion criteria are similar to that used for other spinal cord stimulation surgeries and include anticoagulant therapy, alcohol abuse, inadequate compliance, psychiatric disturbances, active psychosis and major untreated depression [42,43]. Lead location is always subcutaneous. Placing the electrode in subcutaneous plane is extremely important as an electrode very close to dermis will cause pinching and will worsen the pain and an electrode very deep will stimulate the muscles and cause twitching. In a contoured area like thoracic wall, the ON-Q® Tunneler (Braun, Melsungen, Germany) is very helpful as it can be pre-shaped to fit the contour of thoracic wall, the blunt tip of it helps stay in subcutaneous plane and minimal tissue separation does not cause unwanted hematomas. The leads can be placed to bracket the area of pain as shown in Figs. 1 and 3. If the area is large, four contact leads can be used (Fig. 3) and if the area is small two eight contact leads can be used (Fig. 1). Bracketing is helpful in patients with extreme allodynia as placing an electrode directly below the patch of pain can aggravate the pain. In patients with some hyperalgesia and minimal
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allodynia the leads can be placed below the area of pain as shown in Figs. 2 and 4. Preservation of some sensations with functioning vibrotactile receptors in the distribution of pain is mandatory for PFNS therapy to be effective [44]. 4.5. Programming Programming is done using large bipolar configuration. In patients with a lot of subcutaneous fat sometimes longer guarded configurations can be used. The pulse width is always small in the range of 60–120. Larger pulse widths can cause pinching. The best rate is 40 or 50 Hz. In general lower rates are better tolerated. The usual amplitudes needed are between 0.5 and 2 mAmps. Sometimes cycling also helps. 4.6. Mechanism of action Though there are a lot of hypothesized mechanisms of PFNS such as altering local blood flow, blocking cellular depolarization and nerve conduction, alteration in neurotransmitters potency, blocking the nociceptive input to the spinal cord, increasing the production of endogenous endorphins and decreasing the pain threshold [12,38], we do not know the exact mechanism of action. 5. Conclusions Peripheral field stimulation for the treatment of post herpetic neuropathic pain is a safe and effective method for pain relief for an extremely complex problem with very few solutions. Surgical planning and technique are essential for the success of treatment. However, long term prospective randomized controlled trials are required to validate the efficacy of this treatment modality in patients with this clinical conundrum. Conflict of interest None of the co-authors report any conflict of interest. References [1] Weaver BA. The burden of herpes zoster and postherpetic neuralgia in the United States. J Am Osteopath Assoc Mar 2007;107(3 Suppl 1):S2–7. [2] Dworkin RH, Portenoy RK. Proposed classification of herpes zoster pain. Lancet Jun 25 1994;343(8913):1648. [3] Desmond RA, Weiss HL, Arani RB, et al. Clinical applications for change-point analysis of herpes zoster pain. J Pain Symptom Manage Jun 2002;23(6):510–6. [4] Fields HL, Rowbotham M, Baron R. Postherpetic neuralgia: irritable nociceptors and deafferentation. Neurobiol Dis 1998;5(4):209–27. [5] Rowbotham MC, Yosipovitch G, Connolly MK, Finlay D, Forde G, Fields HL. Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis 1996;3(3):205–14. [6] Baron R, Saguer M. Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain: J Neurol Dec 1993;116(Pt 6):1477–96. [7] Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2004;63(September (6)):959–65. [8] Kotani N, Kushikata T, Hashimoto H, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med 2000;343(November (21)):1514–9. [9] Nizard J, Lefaucheur JP, Helbert M, de Chauvigny E, Nguyen JP. Non-invasive stimulation therapies for the treatment of refractory pain. Discov Med 2012;14(July (74)):21–31. [10] Nizard J, Raoul S, Nguyen JP, Lefaucheur JP. Invasive stimulation therapies for the treatment of refractory pain. Discov Med 2012;14(October (77)):237–46. [11] Cruccu G, Aziz TZ, Garcia-Larrea L, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007;14(September (9)):952–70. [12] Surjya Prasad U, Shiv Pratap R, Mishra S, Bhatnagar S. Successful treatment of an intractable postherpetic neuralgia (PHN) using peripheral nerve field stimulation (PNFS). Am J Hosp Palliat Care 2010;27(February (1)):59–62.
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Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Peripheral field stimulation for thoracic post herpetic neuropathic pain Zion Zibly 1 , Mayur Sharma 1 , Andrew Shaw, Milind Deogaonkar ∗ Department of Neurosurgery, Center of Neuromodulation, Wexner Medical Center, The Ohio State University, Columbus, USA
a r t i c l e
i n f o
Article history: Received 11 June 2014 Received in revised form 3 September 2014 Accepted 12 October 2014 Keywords: Peripheral field stimulation Neuromodulation Thoracic Post-herpetic Neuropathic pain
a b s t r a c t Objective: Post herpetic neuralgia is a chronic, debilitating pain with very few management options and is often refractory to treatment. We present our experience with a series of 4 patients who underwent subcutaneous peripheral field stimulation for treatment of thoracic post herpetic neuropathic pain. Methods: Four patients with intractable thoracic post herpetic neuropathic pain were operated after maximum medical treatment and a neuropsychological evaluation. Multiple percutaneous electrodes were placed in the subcutaneous plane in the region of pain for a 7-day trial. Following a successful trial (more than 50% reduction of pain), the electrodes were then internalized and attached to a pulse generator. Visual analog scores (VAS) were studied during the preoperative, immediate postoperative and last follow-up visits. Long-term treatment results were determined by retrospective review of medical records. Average follow-up period was 28.2 months. Results: All 4 patients showed persistent improvement in their VAS pain scores with an average improvement of more than 75%. There were no treatment failures and no complication requiring re-operation was reported. Conclusion: Peripheral field stimulation for the treatment of post herpetic neuropathic pain is a safe and effective method for pain relief for an extremely complex problem with very few solutions. Patient selection and proper lead placement is most important for the success of treatment. © 2014 Published by Elsevier B.V.
1. Introduction Post herpetic neuralgic (PHN) pain is a prevalent chronic neuropathic pain. It follows the eruption of varicella herpes zoster virus (VZV, chickenpox). It is estimated that 1 million new cases of VZV are reported annually in the United States alone [1]. Of those approximately 20–30% will develop PHN. The disorder is defined by three distinctive groups. Acute herpetic neuralgia that develops within 30 days of rash onset, sub-acute herpetic neuralgia which develops within 30–120 days after rash onset and post herpetic neuralgia which is defined as pain lasting at least 120 days following rash onset [2,3]. PHN leads to significant morbidity, diminished
Abbreviations: PFS, peripheral field stimulation; PHN, post-herpetic neuralgia; VZV, Varicella zoster virus; VAS, visual analog scale; IPG, implantable pulse generator. ∗ Corresponding author at: Center of Neuromodulation, Wexner Medical center, The Ohio State University, 480 Medical Center Drive Columbus, OH 43210, USA. Tel.: +1 614 366 2420; fax: +1 614 366 8779. E-mail address: [email protected] (M. Deogaonkar). 1 These authors contributed equally. http://dx.doi.org/10.1016/j.clineuro.2014.10.009 0303-8467/© 2014 Published by Elsevier B.V.
quality of life and decreased productivity. Typically PHN presents as variable pain (moderate to severe) and described by patients as burning, stabbing, shooting or gnawing. The involved area usually presents a dermatome belt of one or more nerves and there might be skin color changes or scarring [4,5]. Mostly, physical examination reveals tactile allodynia [6]. Management of PHN consists of Tricyclic antidepressants, anticonvulsants, morphine and lidocaine patches. These treatment offer moderate success and some patients will continue to have chronic PHN pain [7]. Combination therapy of topical capsaicin and aspirin creams was also reported as well as intrathecal methylprednisolone [7,8]. Various non-invasive [transcutaneous electrical nerve stimulation (TENS), repetitive Transcranial Magnetic Stimulation (rTMS), and transcranial direct current stimulation (tDCS)] and invasive [peripheral nerve stimulation (PNS), peripheral field stimulation (PFS), nerve root stimulation (NRS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and motor cortex stimulation (MCS)] neurostimulation techniques have been explored in patients with medical refractory pain syndromes with varied success[9–11]. Due to the success of peripheral field stimulation (PFS) in the treatment of variety of neuropathic pain, there have been few reports of treating PHN via PFS [12–16].
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Here we report our experience with a series of 4 cases of refractory thoracic PHN that were successfully treated with PFS. 2. Methods 2.1. Patient selection Following approval from our institutional review board, a retrospective review of 4 patients with thoracic PHN who were treated with PFS between 2010 and 2013 was done. All patients were referred by pain management specialists in our institution and one by another facility. All the patients were diagnosed to have classical symptoms of PHN and were non responsive to multiple pharmacological medical therapy and other interventions such as nerve blocks. Prior to surgical intervention neuropsychologist confirmed patients to be free of narcotic overuse and psychiatric comorbidities. The pain was assessed using a visual analog scale (VAS) which is a reliable non-verbal measurement scale (10 cm scale, with “0” being considered as “no pain” and “10” being “worst imaginable pain”) commonly used to assess pain and disability [17,18] The neuropsychological evaluation was performed using battery for health improvement inventory (BHI-2), the pain Catastrophizing Scale (PCS) and various pain management instruments as part of comprehensive evaluation. In addition, scores on measures of depression, anxiety and hostility as well as alcohol or illicit drug dependence were evaluated in all patients prior to implantation. The average age of the patient at PFS implantation surgery was 47.5 ± 8.75 years. Half of the patients were males. All patients underwent a PFS trial done by our team. The 7-day trial period was used in order to confirm at least 50% reduction in the pain VAS score. Following successful PFS trial the patients underwent implantation of permanent lead stimulator and a pulse generator.
Fig. 1. Two octode PFS leads bracketing the area of PHN pain on the right anterior thoracic wall.
2.2. Surgical technique As described in patient selection, surgery is done as a two stage procedure. For the trial procedure, the patient is awake. Area of pain and allodynia is marked before induction of local anesthesia and sedation. The surgical site is prepped and draped. A small skin puncture is made with a Tuohy needle. ON-Q® tunneler (I-Flow, Lake Forest, CA) that is molded to match the curvature of the thoracic region is introduced into the subcutaneous place by virtue of its flexibility and atraumatic tip. Four or eight contact cylindrical leads [Quad, Octad, Quad Plus, or Quad Compact (Medtronic, Inc, Minneapolis, MN)] are placed in the region of pain that is demarcated preoperatively in the same plane. We preferentially use an ON-Q tunneler (I-Flow, Lake Forest, CA) for the placement of cylindrical leads. The direction of tunneling and placing the lead is chosen to be either along the border of pain if there is significant allodynia or underlying the area of pain if allodynia is minimal. Leads are then anchored with a skin stitch. Trial stimulation with externalized battery is then carried out for 7 days. In case of successful trial (more than 50% improvement in pain), permanent implant is done along with an implantable pulse generator (IPG) placement (Activa SC or Activa RC; Medtronic, Inc, Minneapolis, MN). The permanent implant is similar to trial lead placement, except the leads are placed using small skin incisions and are anchored subcutaneously and then tunneled to the IPG site (Figs. 1–4). A rechargeable IPG is placed in an IPG pocket either in infraclavicular region or over abdominal wall or over the hip.
Fig. 2. Three PFS leads (2 quads and 1 octode) below the area of PHN pain on the left anterior and posterior thoracic wall and implantable pulse generator in the left subclavicular region.
2.3. Pain assessment, functional status and data collection Following implantation of the PFS, patients were scheduled for an immediate post-operative visit at 10 days and then outpatient
Fig. 3. Four quad PFS leads bracketing the area of PHN pain on the left anterior and posterior thoracic wall.
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at the last follow up was 2.5 ± 1.3. The average reduction in VAS score was 6.5 ± 1 or 72%. The highest reduction in VAS score was 8 (88%) whereas the lowest was 6 (67%). Patients reported impressive improvement in their quality of life, social activity, return to work and activities as compared to pre PHN pain. Case 4 had already retired. All patients reported more than 80% area coverage by stimulation.
3.3. Adverse events During the follow up period there were no reports of either major or minor complications that required reoperation.
4. Discussion 4.1. PHN: the scope of problem
Fig. 4. Two octode PFS leads below the area of PHN pain on the anterior thoracic wall and implantable pulse generator in the buttock region.
clinic visits as needed for programming. During these visits programming of the stimulation setting was done as needed and VAS recorded. Functional status was assessed by patients’ report of returning to work, social activity and their return to daily activities as prior to occurrence of the PHN. 3. Results 3.1. Patients demographics The demographic characteristic of patients (n = 4) with postherpetic neuralgia who underwent PFS implantation surgery is mentioned in Table 1. Prior history of VZV and PHN was well documented in all four patients. The location of the PHN in all 4 patients was along the thoracic dermatome distribution. Duration of PHN was 3–8 years. Two patients had allodynia and two had hyperalgesia with minimal allodynia that required placement of leads below the area of pain. None of the patients in our series had hypoesthesia or anesthesia in the region of pain (anesthesia dolorosa/deafferentiation pain). Average period of follow up was 28.25 ± 11.6 months (min 5 months, max 36 months). 3.2. VAS changes Average VAS score at baseline was 9, with lowest VAS score of 7 and highest VAS score of 10. Average immediate post op VAS was 2 indicating a reduction of 78% (Fig. 5). The average VAS score
Post herpetic neuralgia (PHN) is one of the most challenging chronic neuropathic pain syndromes. It is also the third most common cause of neuropathic pain in the United States [1,19]. PHN is defined as pain persisting for more than 4 months after the onset of herpes zoster rash [12,20]. PHN pain also seems to be more severe in patients who present with sensory disturbances, allodynia and hyperalgesia, when compared to other types of neuropathic pain [21]. Patients with PHN presents with constant burning, throbbing, arching type of pain or intermittent sharp, shooting pain with tactile allodynia [12,22]. The reactivation of dormant varicella zoster virus causes inflammation of the sensory ganglia and peripheral nerves and thereby inducing abnormal sensitization and hyperexcibility [4]. This reactivation generally occurs in elderly immunodeficient patients or following stressful episodes [22,23]. There are three distinct pathophysiological mechanisms which can explain the symptomatology associated with PHN, first constant firing from abnormally hyperactive but anatomically intact primary afferent nociceptors resulting in central hypersensitization with allodynia [4,12,22,24,25]; Second, loss of C-nociceptors and fibers that initiate central sprouting of A-beta fibers, which make contact with the nociceptors leading to hyperalgesia and allodynia [4,12,22,26]; third, loss of both large and small diameter fibers generates spontaneous activity in deafferented central neurons and produce constant pain in the region of profound sensory deficits without allodynia (anesthesia dolorosa) [4,12,22]. Due to the interplay of these mechanisms in the generation of PHN, a single treatment modality might not be effective and therefore in the majority of patients multidrug regimens are required to achieve pain relief of >50%. Various pharmacological measures such as tricyclic antidepressants, anticonvulsants (pregablin and gabapentin), morphine sulphate, tramadol, controlled release oxycodone, lidocaine patches, topical capsaicin, continues subcutaneous ketamine infusion and intrathecal methylprednisolone have been proved to be efficacious in controlling the pain associated with PHN [7,8,27]. Spinal cord stimulation (SCS) was also described and used for the treatment of PHN. Harke et al. described a series of 28 patients who were treated with SCS for PHN and reported pain relief in 82% of the studied group [22]. However despite the availability of these pharmacological and surgical measures, a significant number of patients do not achieve adequate pain relief. The postulated mechanisms of the failure of pharmacotherapy in PHN are potential ineffectiveness, intolerability due to significant side effects, tolerance and inability to administer optimal dosage especially in elderly patients with significant cardiac and CNS comorbidities [22,28].
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Table 1 Demographic characteristic of patients (n = 4) with post-herpetic neuralgia who underwent PFS implantation surgery. Patient
Age in yrs./Gender
History of VZV and PHN
Location of PHN
Preoperative VAS score
Immediate Postoperative VAS score
Postoperative VAS score at last follow up
Adverse events
Patient 1
43/Female
Yes
10/10
2/10
2/10
None
Patient 2
38/Male
Yes
9/10
3/10
3/10
None
Patient 3
44/Male
Yes
10/10
4/10
4/10
None
Patient 4
65/Female
Yes
Thoracic (T6-12). Thoracic (T10-12) Thoracic (T9-12). Thoracic (T10-12)
7/10
0/10
1/10
None
PFS: peripheral field stimulation; VZV: varicella zoster virus; PHN: post-herpetic neuralgia; VAS: visual analog scale (min = 0, no pain; max = 10, worst pain).
Fig. 5. Preoperative and postoperative (following PFS implantation surgery) pain intensity on visual analog scale (VAS) in four patients with PHN.
4.2. Role of PFS in treatment of PHN The first description of electric stimulation of the peripheral nerves by implanting electrodes for the relieve of chronic cutaneous pain in four patients was reported by Wall et al. in 1967 [29]. PFS has been used for the treatment of a variety of chronic neuropathic pain syndromes such as cervicogenic headaches, migraines [16,30–34], atypical trigeminal neuralgia or facial pain [35], chronic shoulder pain [36], diabetic neuropathic and chronic abdominal pain [12,37,38]. As regards PFS for the treatment of cutaneous PHN, there have been only case reports. Surjya et al. reported successful treatment in a patient who developed painful supra orbital PHN following chemotherapy [12]. In their study, the authors reported 100% reduction in pain intensity during an 8-week follow up. They also reported that the patient was free of all pain management following implantation of the PFS. Kouroukli et al. reported two cases of thoracic PHN treated with PFS who had dramatic reduction in pain [39]. In a randomized trial reported by Guiseppe et al., patients who presented with PHN were treated with Scrambler therapy, which is a noninvasive superficial electric stimulation [40,41]. In this study, the group of patients treated with the electric stimulation showed much higher reduction of pain. 4.3. Our experience Our series included four patients who presented with thoracic PHN. To the best of knowledge this is the largest number of patients treated with PFS. The location of the pain was thoracic in all four. Average immediate post op VAS reduction was 78% (Fig. 5). The average VAS score at the last follow up was 72%. The highest reduction in VAS score was 88% whereas the lowest was 70%. Patients reported improvement in their quality of life, social activity, return
to work and activities. This study presents the longest follow up period for PNFS for the treatment of PHN. The advantages of PFS are minimally invasive procedure, focused stimulation and no spillover of stimulation to other areas. With spinal cord stimulation it is very difficult to cover the axial narrow areas of pain as in PHN and there is a large unwanted and often annoying spillover of stimulation to other areas of trunk or extremities. 4.4. Patient selection and lead location Patient selection and lead location planning are the key factors for good clinical outcome. The exclusion criteria are similar to that used for other spinal cord stimulation surgeries and include anticoagulant therapy, alcohol abuse, inadequate compliance, psychiatric disturbances, active psychosis and major untreated depression [42,43]. Lead location is always subcutaneous. Placing the electrode in subcutaneous plane is extremely important as an electrode very close to dermis will cause pinching and will worsen the pain and an electrode very deep will stimulate the muscles and cause twitching. In a contoured area like thoracic wall, the ON-Q® Tunneler (Braun, Melsungen, Germany) is very helpful as it can be pre-shaped to fit the contour of thoracic wall, the blunt tip of it helps stay in subcutaneous plane and minimal tissue separation does not cause unwanted hematomas. The leads can be placed to bracket the area of pain as shown in Figs. 1 and 3. If the area is large, four contact leads can be used (Fig. 3) and if the area is small two eight contact leads can be used (Fig. 1). Bracketing is helpful in patients with extreme allodynia as placing an electrode directly below the patch of pain can aggravate the pain. In patients with some hyperalgesia and minimal
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allodynia the leads can be placed below the area of pain as shown in Figs. 2 and 4. Preservation of some sensations with functioning vibrotactile receptors in the distribution of pain is mandatory for PFNS therapy to be effective [44]. 4.5. Programming Programming is done using large bipolar configuration. In patients with a lot of subcutaneous fat sometimes longer guarded configurations can be used. The pulse width is always small in the range of 60–120. Larger pulse widths can cause pinching. The best rate is 40 or 50 Hz. In general lower rates are better tolerated. The usual amplitudes needed are between 0.5 and 2 mAmps. Sometimes cycling also helps. 4.6. Mechanism of action Though there are a lot of hypothesized mechanisms of PFNS such as altering local blood flow, blocking cellular depolarization and nerve conduction, alteration in neurotransmitters potency, blocking the nociceptive input to the spinal cord, increasing the production of endogenous endorphins and decreasing the pain threshold [12,38], we do not know the exact mechanism of action. 5. Conclusions Peripheral field stimulation for the treatment of post herpetic neuropathic pain is a safe and effective method for pain relief for an extremely complex problem with very few solutions. Surgical planning and technique are essential for the success of treatment. However, long term prospective randomized controlled trials are required to validate the efficacy of this treatment modality in patients with this clinical conundrum. Conflict of interest None of the co-authors report any conflict of interest. References [1] Weaver BA. The burden of herpes zoster and postherpetic neuralgia in the United States. J Am Osteopath Assoc Mar 2007;107(3 Suppl 1):S2–7. [2] Dworkin RH, Portenoy RK. Proposed classification of herpes zoster pain. Lancet Jun 25 1994;343(8913):1648. [3] Desmond RA, Weiss HL, Arani RB, et al. Clinical applications for change-point analysis of herpes zoster pain. J Pain Symptom Manage Jun 2002;23(6):510–6. [4] Fields HL, Rowbotham M, Baron R. Postherpetic neuralgia: irritable nociceptors and deafferentation. Neurobiol Dis 1998;5(4):209–27. [5] Rowbotham MC, Yosipovitch G, Connolly MK, Finlay D, Forde G, Fields HL. Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis 1996;3(3):205–14. [6] Baron R, Saguer M. Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain: J Neurol Dec 1993;116(Pt 6):1477–96. [7] Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2004;63(September (6)):959–65. [8] Kotani N, Kushikata T, Hashimoto H, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med 2000;343(November (21)):1514–9. [9] Nizard J, Lefaucheur JP, Helbert M, de Chauvigny E, Nguyen JP. Non-invasive stimulation therapies for the treatment of refractory pain. Discov Med 2012;14(July (74)):21–31. [10] Nizard J, Raoul S, Nguyen JP, Lefaucheur JP. Invasive stimulation therapies for the treatment of refractory pain. Discov Med 2012;14(October (77)):237–46. [11] Cruccu G, Aziz TZ, Garcia-Larrea L, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007;14(September (9)):952–70. [12] Surjya Prasad U, Shiv Pratap R, Mishra S, Bhatnagar S. Successful treatment of an intractable postherpetic neuralgia (PHN) using peripheral nerve field stimulation (PNFS). Am J Hosp Palliat Care 2010;27(February (1)):59–62.
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