Pain, 44 (1991) 131-138 0 1991 Elsevier Science Publishers ADONIS 030439599100066Y
131 B.V. 0304-3959/91/$03.50
PAIN 01724
Study of experimental pain measures and nociceptive reflex in chronic pain patients and normal subjects F. Boureau, M. Luu and J.F. Doubrke Centre d’Evaluation et de Traitement (Received
de In Douleur, Hapital Saint-Antoine,
27 April 1990, revision received
12 July 1990, accepted
Paris (France)
3 August
1990)
This study evaluates (i) the effect of heterotopic chronic pain on various experimental pain measures, Summary (ii) the relationship between experimental pain measures and chronic pain symptomatology assessment, and (iii) the influence of the various pain aetiologies on experimental pain measures. Fifty-three chronic pain patients were compared to 17 pain-free subjects with the following psychophysical and physiological indices: pain threshold (PTh), pain tolerance (PTol), verbal estimation of intensity and unpleasantness (intensity scale, IS; unpleasantness scale, US), threshold for intensity and unpleasantness (ITh and UTh), lower limb RI11 nociceptive reflex (RIIITh and RI11 frequency of occurrence). Chronic pain syndromes included neuropathic pain (n = 12), iodopathic pain (n = 12), myofascial syndromes (n = 9) headache (n = 9), and miscellaneous pain (n = 11). Chronic pain symptomatology was assessed with a visual analogue scale (VAS), a French MPQ adaptation (QDSA), Beck Depression Inventory (BDI), Spielberger State Trait Inventory (STAI) and Eysenck Personality Inventory (EPI). No significant difference was observed between chronic pain patients and pain-free control groups and between patient subgroups for PTh, PTol and RIIITh. No significant correlation was found between experimental pain measures and clinical pain, anxiety or depression scores. However, the chronic pain patients had a higher threshold for unpleasantness and judged the suprathreshold stimuli significantly less intense and less unpleasant than the control group. These results are discussed in relation to diffuse noxious inhibitory controls and the adaptation level theory of chronic pain experience. Key words: Chronic pain; Electrical stimulation; tolerance
Magnitude estimation:
Introduction
Clinical pain involves perceptual, affective, cognitive, evaluative and behavioral factors 112,281. Clinical pain assessment must rely on subjective or behavioral variables since available measurements of the peripheral or central generators are lacking. In contrast, in the laboratory, noxious stimuli and verbal responses (or other physiological indices) can be quantified. The introduction of experimental pain in the clinical setting may
Correspondence to: Dr. Franqois Boureau, Centre d’Evaluation et de Traitement de la Douleur, H&pita1 Saint Antoine, 184 Rue du Fg. St.-Antoine, 75012 Paris, France.
Nociceptive
reflex; Pain threshold;
Pain
gain more objectivity, permitting, for example, parallel study of treatments on clinical and experimental pain. However, the physiological or psychological mechanisms by which a clinical pain sensation may influence the transmission of experimental pain information or the perceptual processes are not fully understood. Several different physiological and/or psychological factors can be involved in the influence of clinical pain on experimental measures. Various studies [5,10,13] have assessed thresholds in the segmental distribution of the pain, while other studies [4,7,8,13-15,17,19,20,23,27,33,35,36,42] mainly focus on extrasegmental distant effects of clinical pain. In the clinical conditions, one might expect cutaneous sensibility dysfunction (i.e., hyperalgesia, allodynia.. .) in the
pain area. The corresponding underlying neurophysiologicat mechanism most probably implicates convergence of excitatory information on spinal or supraspinal neurons which could result in lowered thresholds to different stimuli. including pain. applied in the metameric area. In contrast to these intrasegmental changes, other possible extrasegmental effects could be related to mechanisms such as diffuse noxious inhibitory controls (DNICs) [1X]. Heterotopic (i.e., distant) pain-relieving effects, evoked by noxious stimuli applied to widespread areas of the body, have been described in animals [18] and humans f39]. DNICs affect activities from convergent (or wide-dynamic-range) neurons evoked by noxious stimulation and are mediated by a loop which ascends to supraspinal structures within the ventrolateral quadrant and descends within the dorsolateral funiculus [18,39,40]. From a psychological point of view, two different conceptual models have theorized the possible influence of clinical pain on pain measures. Chapman [6] hypothesized that patients with persistent pain, because of social reinforcement, would develop perceptual habits of hype~igilance for somatic distress signals. This exaggerated focus on internal sensations may shift nonpainful sensations to pain. The clinical implications of the hypervigilance model may be related to the stimulus generalization theory of Fordyce [9]. Stimulus generalization states that a particular response which is at first linked to a specific stimulus could after some time generalize to other stimuli (i.e., proprioceptive sensations, stressful situations). According to the hypervigilance and stimulus generalization models, chronic pain patients when receiving an acute experimental stimulus would react with exaggerated reactivity and would have decreased pain threshold and/or pain tolerance in comparison with a control group. In contrast with the above hypothesis, Rollman [31] suggested that pain patients would evaluate experimental pain within the context of their previous experience with pain, and proposed an adaptation level theory. According to this model [16,31,32], pain judgments are based on comparisons with other pain levels. This suggests that subjects experiencing chronic pain may utilize their endogenous pain levels as an ‘anchor’ in describing external painful stimuli. This model predicts that, because of their internal discomfort, chronic pain patients should have higher pain threshold and tolerance than controls and should judge external painful stimuli as less severe than would pain-free individuals. Hypervigilance theory and adaptation level theory predict opposite reactivity for chronic pain patients submitted to an experimental stimulus. The present study is mainly concerned with the effects of clinical pain on heterotopic pain measures. Of the 16 related studies reviewed in the literature, 8 [7,14,15,17,20.27,41,42] found that chronic pain experience increased the thresholds to various experimental
pain stimuli, 6 found that chronic pain decreased rather than increased pain threshold [4,19,2?.33.35.36], and 2 found no significant effects [X,13]. Many factors can account for these conflicting results. such as type of stimuli. type of pain disorders. type of pain measures. It has been hypothesized that paradigms with stimuli 01 less clinical relevance make adaptation-level responding more likely [26]. Affective stimuli will elicit adaptationlevel behavior. Because of the conflicting data. we undertook the present study to examine (i) the effect of heterotopic chronic pain on different experimental pain measures including psychological and physiological indices (subjective pain thresholds, pain tolerance. verbal estimation of intensity and unpleasantness of the stimuli, intensity and unpleasantness thresholds and a lower limb nociceptive reflex evoked by electrical stimuli). (ii) the influence of Ihe various chronic pain etiologies on the experimental pain measure changes, and (iii) the relationship between experimental measures and the clinical data (i.e., pain, anxiety and depression levels).
MethtnIs Subjects
The 53 chronic pain patients (CPP, 39 F, 14 M) were recruited from the Saint-Antoine multidisciplinary outpatient pain unit. Inclusion criteria were: pain duration of more than 6 months, clinical pain heterotopic to experimental pain test (i.e., homolateral lower limb), verbal aptitude to correctly complete the verbal assessment, informal agreement to the experimental procedure. Exclusion criteria were: polymedication, strong narcotic intake, lower limb sensory or motor dysfunction. The average age was 49.1 years (range 21-75 years). The mean pain duration was 6.6 years (range 6
TABLE
I
Comparison of chronic pain patients (CPP) and control subjects (CS) according to age. sex ratio (F: M), pain threshold (PTh). pain tolerance (PTol), RI11 threshold (RIIITh). intensity threshold (ITh) and unpleasantness threshold (UTh). Statistical comparison is performed using the Mann and Whitney test. CPP (m
(SD.11
CS
U/U’
Significance
(m tS.D.t)
ITO1
n = 53 49.1 39:14 8.4 (3.9) 17.7 (6.4)
n =I7 31.1 6:ll 8.0 (3.4) 18.6 (4.5)
439,‘461 385/515
N’S NS
RIIlTh
n = 48 12.3 (4.5)
n =I7 12.9 (2.8)
318/446
NS
ITh UTh
n = 32 6.5 (4.0) 8.5 (4.8)
n =17 6.0 (3.0) 5.8 (2.0)
249/294 197/347
NS P ., Dickenson, A.H. and Besson. J.M., Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain, 6 (I9791 283-304. I9 Langermank, M.. Jensen. K.. Jensen. T.S. and Olesen, J., Pressure pain thresholds and thermal nociceptive thresholds in chronic tension-type headache, Pain, 3X (1989) 203-210. 20 Lipman. J.J.. Blumenkopf. B. and Parris, W.C.V. Chronic pain assessment using heat beam dolorimetry. Pain, 30 (1987) 59-67. 21 Luu. M.. Bonnel. A.M. and Boureau. F.. Multidimensional experimental pain study in normal man: combining physiological and psycholo@aI indices, In: R. Dubner et al. (Eds.), Proc. Vth World Congress on Pain, Elsevier Science Publishers. Amsterdam 1988. pp. 375-382. 22 Malow, R.M. and Olson. R.E., Changes in pain perception after treatment for chronic pain, Pain, I1 (1981) 65-72. 23 Malow, R.M., Grimm, L. and Olson, R.E., Differences in pain perception between myofascial pain dysfunction patients and normal subjects: a signal detection analysis. J. Psychosom. Res.. 24 (1980) 303-310. 24 Max, M.B., Culnanz. M., Schafer, SC., Gracely, R.H.. Walther, D.J.. Smoller, B. and Dubner, R., Amitriptyline relives diabetic neuropathy pain in patients with normal or depressed mood, Neurology, 37 (1987) 589-596. 25 Merskey, H. and Evans, P.R., Variations in pain complaint threshold in psychiatric and neurological patients with pain, Pain. 1 (1975) 73-79. 26 Naliboff. B.D. and Cohen, M.J., Psychophysical Iaboratory methods applied to clinical pain patients. In: CR. Chapman and J.D. Loeser (Eds.), Issues in Pain Measurement, Raven Press, New York. 1989. pp. 365-386. 27 Nahboff, B.D.. Cohen, M.J., Schandler. S.O. and Heinrich. R.L.. Signal detection and threshold measures for chronic back pain patients, chronic illness patients and cohort controls to radiant heat stimuli. J. Abnorm. Psychol., 90 (1981) 271-274.
2X Price, D.D., Psychological and Neurai Me~hanI~rns of Pain. Raveu Press, New York. 1988. 241 pp. 29 Price, D.D. and Harkins. SW.. Combined use of experimental pain and visual analogue scales in providing standardized measurement of clinical pain. Clin. J. Pain, 3 (1987) 1 --X. 30 Price. D.D., Harkins, SW.. Radii. A. and Price, C.. A simultaneous comparison of fentanyl’s analgesic effects on experimental and climcal pain, Pain, 24 (1986) 197-203. 31 Rollman. G.B.. Signal detection theory pain measures: empirical validation studies and adaptation-level effects, Pain, 6 (1979) 9-21 32 Rollman, G.B.. Measurements of experimental pain in chronic pain patients: meth~ologica1 and individual factors. In: R. Melzack (Ed.), Pain Measurements and Assessment. Raven Press. New York, 1983, pp. Z-258. 33 Sandrini. G., Martignoni. E.. Micieli, G., Alfonsi, E.. Sances, G. and Nappi. G., Pain reflexes in the ctinical assessment of migraine syndromes, Func. Neural.. 4 (1986) 423-429. 34 Schmidt. A.J.M., The behavioral management of pain: a criticism of a response, Pain. 30 (1987) 2X5-291. 35 Schmidt, A.J.M. and Brands, A.M.E.F., Persistence behavior of chronic low back pain patients in an acute pain situation. J. Psychosom. Res.. 3 (1986) 339-346. 36 Scudds, R.A., Rollman. G.B., Harth, M. and McCain, G.A.. Pain perception and personality measures as discriminators in the classification of fibrositis. J. Rheumatol., 14 (1987) 563-$69. 37 WiIIer. J.C., Comparative study of perceived pain and nociceptive flexion reflex in man. Pain, 3 (1977) 69-80. 38 Witler. J.C., Boureau, F. and Athe-Fessard, D., Supraspinal influences on nociceptive flexion reflex and pain sensation in man, Brain Res.. 179 (1979) 61 -68. 39 Willer, J.C.. Roby. A. and Le Bars, D., Psychophysical and electrophysiological approaches to the pain-relieving effects of heterotopic nociceptive stimuli, Brain. 107 (1984) 1095-1112. 40 Wilier, J.C.. Barranquero. A.. Kahn. M.F. and Salliere, D., Pain in sciatica depresses lower limb nociceptive reflexes to sural nerve stimulation. J. Neurol. Neurosurg. Psychiat.. 50 (1987) l-5. 41 Wolskee, P.J. and Gracely, R.H.. Effect of chronic pain on experimental pain response, Am. Pain Sot.. (1980) Abst. 4: 4. 42 Yang, J.C., Richiin, D.. Brand, L.. Wagner, J. and Clark. W.C.. Thermal sensory decision theory indices and pain thresholds in chronic pain patients and healthy volunteers. Psychosom. Med., 47 (1985) 461-468.
131 B.V. 0304-3959/91/$03.50
PAIN 01724
Study of experimental pain measures and nociceptive reflex in chronic pain patients and normal subjects F. Boureau, M. Luu and J.F. Doubrke Centre d’Evaluation et de Traitement (Received
de In Douleur, Hapital Saint-Antoine,
27 April 1990, revision received
12 July 1990, accepted
Paris (France)
3 August
1990)
This study evaluates (i) the effect of heterotopic chronic pain on various experimental pain measures, Summary (ii) the relationship between experimental pain measures and chronic pain symptomatology assessment, and (iii) the influence of the various pain aetiologies on experimental pain measures. Fifty-three chronic pain patients were compared to 17 pain-free subjects with the following psychophysical and physiological indices: pain threshold (PTh), pain tolerance (PTol), verbal estimation of intensity and unpleasantness (intensity scale, IS; unpleasantness scale, US), threshold for intensity and unpleasantness (ITh and UTh), lower limb RI11 nociceptive reflex (RIIITh and RI11 frequency of occurrence). Chronic pain syndromes included neuropathic pain (n = 12), iodopathic pain (n = 12), myofascial syndromes (n = 9) headache (n = 9), and miscellaneous pain (n = 11). Chronic pain symptomatology was assessed with a visual analogue scale (VAS), a French MPQ adaptation (QDSA), Beck Depression Inventory (BDI), Spielberger State Trait Inventory (STAI) and Eysenck Personality Inventory (EPI). No significant difference was observed between chronic pain patients and pain-free control groups and between patient subgroups for PTh, PTol and RIIITh. No significant correlation was found between experimental pain measures and clinical pain, anxiety or depression scores. However, the chronic pain patients had a higher threshold for unpleasantness and judged the suprathreshold stimuli significantly less intense and less unpleasant than the control group. These results are discussed in relation to diffuse noxious inhibitory controls and the adaptation level theory of chronic pain experience. Key words: Chronic pain; Electrical stimulation; tolerance
Magnitude estimation:
Introduction
Clinical pain involves perceptual, affective, cognitive, evaluative and behavioral factors 112,281. Clinical pain assessment must rely on subjective or behavioral variables since available measurements of the peripheral or central generators are lacking. In contrast, in the laboratory, noxious stimuli and verbal responses (or other physiological indices) can be quantified. The introduction of experimental pain in the clinical setting may
Correspondence to: Dr. Franqois Boureau, Centre d’Evaluation et de Traitement de la Douleur, H&pita1 Saint Antoine, 184 Rue du Fg. St.-Antoine, 75012 Paris, France.
Nociceptive
reflex; Pain threshold;
Pain
gain more objectivity, permitting, for example, parallel study of treatments on clinical and experimental pain. However, the physiological or psychological mechanisms by which a clinical pain sensation may influence the transmission of experimental pain information or the perceptual processes are not fully understood. Several different physiological and/or psychological factors can be involved in the influence of clinical pain on experimental measures. Various studies [5,10,13] have assessed thresholds in the segmental distribution of the pain, while other studies [4,7,8,13-15,17,19,20,23,27,33,35,36,42] mainly focus on extrasegmental distant effects of clinical pain. In the clinical conditions, one might expect cutaneous sensibility dysfunction (i.e., hyperalgesia, allodynia.. .) in the
pain area. The corresponding underlying neurophysiologicat mechanism most probably implicates convergence of excitatory information on spinal or supraspinal neurons which could result in lowered thresholds to different stimuli. including pain. applied in the metameric area. In contrast to these intrasegmental changes, other possible extrasegmental effects could be related to mechanisms such as diffuse noxious inhibitory controls (DNICs) [1X]. Heterotopic (i.e., distant) pain-relieving effects, evoked by noxious stimuli applied to widespread areas of the body, have been described in animals [18] and humans f39]. DNICs affect activities from convergent (or wide-dynamic-range) neurons evoked by noxious stimulation and are mediated by a loop which ascends to supraspinal structures within the ventrolateral quadrant and descends within the dorsolateral funiculus [18,39,40]. From a psychological point of view, two different conceptual models have theorized the possible influence of clinical pain on pain measures. Chapman [6] hypothesized that patients with persistent pain, because of social reinforcement, would develop perceptual habits of hype~igilance for somatic distress signals. This exaggerated focus on internal sensations may shift nonpainful sensations to pain. The clinical implications of the hypervigilance model may be related to the stimulus generalization theory of Fordyce [9]. Stimulus generalization states that a particular response which is at first linked to a specific stimulus could after some time generalize to other stimuli (i.e., proprioceptive sensations, stressful situations). According to the hypervigilance and stimulus generalization models, chronic pain patients when receiving an acute experimental stimulus would react with exaggerated reactivity and would have decreased pain threshold and/or pain tolerance in comparison with a control group. In contrast with the above hypothesis, Rollman [31] suggested that pain patients would evaluate experimental pain within the context of their previous experience with pain, and proposed an adaptation level theory. According to this model [16,31,32], pain judgments are based on comparisons with other pain levels. This suggests that subjects experiencing chronic pain may utilize their endogenous pain levels as an ‘anchor’ in describing external painful stimuli. This model predicts that, because of their internal discomfort, chronic pain patients should have higher pain threshold and tolerance than controls and should judge external painful stimuli as less severe than would pain-free individuals. Hypervigilance theory and adaptation level theory predict opposite reactivity for chronic pain patients submitted to an experimental stimulus. The present study is mainly concerned with the effects of clinical pain on heterotopic pain measures. Of the 16 related studies reviewed in the literature, 8 [7,14,15,17,20.27,41,42] found that chronic pain experience increased the thresholds to various experimental
pain stimuli, 6 found that chronic pain decreased rather than increased pain threshold [4,19,2?.33.35.36], and 2 found no significant effects [X,13]. Many factors can account for these conflicting results. such as type of stimuli. type of pain disorders. type of pain measures. It has been hypothesized that paradigms with stimuli 01 less clinical relevance make adaptation-level responding more likely [26]. Affective stimuli will elicit adaptationlevel behavior. Because of the conflicting data. we undertook the present study to examine (i) the effect of heterotopic chronic pain on different experimental pain measures including psychological and physiological indices (subjective pain thresholds, pain tolerance. verbal estimation of intensity and unpleasantness of the stimuli, intensity and unpleasantness thresholds and a lower limb nociceptive reflex evoked by electrical stimuli). (ii) the influence of Ihe various chronic pain etiologies on the experimental pain measure changes, and (iii) the relationship between experimental measures and the clinical data (i.e., pain, anxiety and depression levels).
MethtnIs Subjects
The 53 chronic pain patients (CPP, 39 F, 14 M) were recruited from the Saint-Antoine multidisciplinary outpatient pain unit. Inclusion criteria were: pain duration of more than 6 months, clinical pain heterotopic to experimental pain test (i.e., homolateral lower limb), verbal aptitude to correctly complete the verbal assessment, informal agreement to the experimental procedure. Exclusion criteria were: polymedication, strong narcotic intake, lower limb sensory or motor dysfunction. The average age was 49.1 years (range 21-75 years). The mean pain duration was 6.6 years (range 6
TABLE
I
Comparison of chronic pain patients (CPP) and control subjects (CS) according to age. sex ratio (F: M), pain threshold (PTh). pain tolerance (PTol), RI11 threshold (RIIITh). intensity threshold (ITh) and unpleasantness threshold (UTh). Statistical comparison is performed using the Mann and Whitney test. CPP (m
(SD.11
CS
U/U’
Significance
(m tS.D.t)
ITO1
n = 53 49.1 39:14 8.4 (3.9) 17.7 (6.4)
n =I7 31.1 6:ll 8.0 (3.4) 18.6 (4.5)
439,‘461 385/515
N’S NS
RIIlTh
n = 48 12.3 (4.5)
n =I7 12.9 (2.8)
318/446
NS
ITh UTh
n = 32 6.5 (4.0) 8.5 (4.8)
n =17 6.0 (3.0) 5.8 (2.0)
249/294 197/347
NS P ., Dickenson, A.H. and Besson. J.M., Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain, 6 (I9791 283-304. I9 Langermank, M.. Jensen. K.. Jensen. T.S. and Olesen, J., Pressure pain thresholds and thermal nociceptive thresholds in chronic tension-type headache, Pain, 3X (1989) 203-210. 20 Lipman. J.J.. Blumenkopf. B. and Parris, W.C.V. Chronic pain assessment using heat beam dolorimetry. Pain, 30 (1987) 59-67. 21 Luu. M.. Bonnel. A.M. and Boureau. F.. Multidimensional experimental pain study in normal man: combining physiological and psycholo@aI indices, In: R. Dubner et al. (Eds.), Proc. Vth World Congress on Pain, Elsevier Science Publishers. Amsterdam 1988. pp. 375-382. 22 Malow, R.M. and Olson. R.E., Changes in pain perception after treatment for chronic pain, Pain, I1 (1981) 65-72. 23 Malow, R.M., Grimm, L. and Olson, R.E., Differences in pain perception between myofascial pain dysfunction patients and normal subjects: a signal detection analysis. J. Psychosom. Res.. 24 (1980) 303-310. 24 Max, M.B., Culnanz. M., Schafer, SC., Gracely, R.H.. Walther, D.J.. Smoller, B. and Dubner, R., Amitriptyline relives diabetic neuropathy pain in patients with normal or depressed mood, Neurology, 37 (1987) 589-596. 25 Merskey, H. and Evans, P.R., Variations in pain complaint threshold in psychiatric and neurological patients with pain, Pain. 1 (1975) 73-79. 26 Naliboff. B.D. and Cohen, M.J., Psychophysical Iaboratory methods applied to clinical pain patients. In: CR. Chapman and J.D. Loeser (Eds.), Issues in Pain Measurement, Raven Press, New York. 1989. pp. 365-386. 27 Nahboff, B.D.. Cohen, M.J., Schandler. S.O. and Heinrich. R.L.. Signal detection and threshold measures for chronic back pain patients, chronic illness patients and cohort controls to radiant heat stimuli. J. Abnorm. Psychol., 90 (1981) 271-274.
2X Price, D.D., Psychological and Neurai Me~hanI~rns of Pain. Raveu Press, New York. 1988. 241 pp. 29 Price, D.D. and Harkins. SW.. Combined use of experimental pain and visual analogue scales in providing standardized measurement of clinical pain. Clin. J. Pain, 3 (1987) 1 --X. 30 Price. D.D., Harkins, SW.. Radii. A. and Price, C.. A simultaneous comparison of fentanyl’s analgesic effects on experimental and climcal pain, Pain, 24 (1986) 197-203. 31 Rollman. G.B.. Signal detection theory pain measures: empirical validation studies and adaptation-level effects, Pain, 6 (1979) 9-21 32 Rollman, G.B.. Measurements of experimental pain in chronic pain patients: meth~ologica1 and individual factors. In: R. Melzack (Ed.), Pain Measurements and Assessment. Raven Press. New York, 1983, pp. Z-258. 33 Sandrini. G., Martignoni. E.. Micieli, G., Alfonsi, E.. Sances, G. and Nappi. G., Pain reflexes in the ctinical assessment of migraine syndromes, Func. Neural.. 4 (1986) 423-429. 34 Schmidt. A.J.M., The behavioral management of pain: a criticism of a response, Pain. 30 (1987) 2X5-291. 35 Schmidt, A.J.M. and Brands, A.M.E.F., Persistence behavior of chronic low back pain patients in an acute pain situation. J. Psychosom. Res.. 3 (1986) 339-346. 36 Scudds, R.A., Rollman. G.B., Harth, M. and McCain, G.A.. Pain perception and personality measures as discriminators in the classification of fibrositis. J. Rheumatol., 14 (1987) 563-$69. 37 WiIIer. J.C., Comparative study of perceived pain and nociceptive flexion reflex in man. Pain, 3 (1977) 69-80. 38 Witler. J.C., Boureau, F. and Athe-Fessard, D., Supraspinal influences on nociceptive flexion reflex and pain sensation in man, Brain Res.. 179 (1979) 61 -68. 39 Willer, J.C.. Roby. A. and Le Bars, D., Psychophysical and electrophysiological approaches to the pain-relieving effects of heterotopic nociceptive stimuli, Brain. 107 (1984) 1095-1112. 40 Wilier, J.C.. Barranquero. A.. Kahn. M.F. and Salliere, D., Pain in sciatica depresses lower limb nociceptive reflexes to sural nerve stimulation. J. Neurol. Neurosurg. Psychiat.. 50 (1987) l-5. 41 Wolskee, P.J. and Gracely, R.H.. Effect of chronic pain on experimental pain response, Am. Pain Sot.. (1980) Abst. 4: 4. 42 Yang, J.C., Richiin, D.. Brand, L.. Wagner, J. and Clark. W.C.. Thermal sensory decision theory indices and pain thresholds in chronic pain patients and healthy volunteers. Psychosom. Med., 47 (1985) 461-468.
