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Psychophysics / Hyperalgesia

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EFFECTS OF PERORAL AND TOPICAL IBUPROFEN UPON LOW PH-INDUCED CUTANEOUS AND MUSCLE PAIN

A E Steen. P. W Reeh, G Geisslinger*, K H Steen. Dept of Dermatology, Univ. Bonn, D-53105 Bonn, Germany

Aim of Investigation Epidermal applications are still gaining popularity in the treatment of cutaneous pain and of painful disorders in joints and muscle. The low pH-pain model in human skin has previously been able to demonstrate effects of antipyretic analgesics in dose dependent manner and to establish time-action profiles Here, we examined the analgesic action ofibuprofen after epidermal application and compared the effects with oral administration

Methods The two studies (with n = 12 subjects each) were performed double blind, randomized, and with one week interval between cross-over In study 1 the volunteers underwent mtradermal infusions with isotonic phosphate buffered solution ofpH52 and synchronously received either 800 mg ibuprofen per os and topical placebo or 4 g of a 5% commercial ibuprofen gel topically applied and oral placebo caps, respectively In study 2 the same protocol was applied with painful intramuscular infusion of isotonic phosphate buffer

Results The flow rate of the pH-mfusion was adjusted to induce a pain magnitude of 20% on a visual analog scale (ranging from "no" (0%) to "unbearable pain" (100%)) For that higher flow rates were needed in the muscle than in the skin Ibuprofen (S-, R-) plasma levels after oral administrations were measured with the HPLC method, and after topical applications gas-chromatography combined with mass-spectroscopy were needed to determine plasma levels in the range ofng/ml In the cutaneous model after the topical verum gel, pain ratings decreased to zero within the observation time of 55 mm Pain reduction after peroral ibuprofen caps reached a similar magnitude of effect, but was slower to develop In the muscle model the commercial ibuprofen gel was not able to significantly reduce the pain in the acidic muscle, but also the 800 mg ibuprofen were not as effective, though significant in pain-reduction within 55 mm as in the skin model. Reasons for the differential susceptibility of cutaneous versus muscular acidosis pain to ibuprofen have yet to be found

Acknowledgments This work was supported by the Deutsche Forschungsgememschaft, grant Ste593/l-3

LOW PH-INDUCED PAIN IN HUMAN SKIN IS ENHANCED BY PROSTAGLANDIN E

K. H Steen. A Sidiropoulos*, H Wegner* Dept of Dermatology, Univ Bonn, D-53105 Bonn, Germany

Aim of Investigation and Methods An ample combination of inflammatory mediators including prostaglandm has been shown to potentiate the pain from experimental tissue acidosis in human skin (Steen et al , Pain 66 (1996) 163-70) The present psychophysical study focused on the role ofprostaglandm E; (PGE;), using bolus injections (0 1 ml), and continuous infiltration of the skin with buffered solutions through indwelling mtradermal canulas in double-blind cross-over sessions with 9 volunteers

Results: PGE; injections (10 'M at pH 7 4) induced strong itching sensations possibly reflecting mast cell degranulation In skin infused with neutral buffer as well as in skin made acidotic all acid bolus injections (pH 6.1) produced a sharp transient burning pain, which was markedly stronger and longer lasting in acidic skin, if PGE; was contained in the bolus instead of the plain acid vehicle (144% increase, p<0.0002, U-test) In neutral skin, acidic PGE; injections were less painful and the discrepancy to vehicle injections was smaller (50% increase, p<0 0002, U-test) Successive bolus injections of acidic PGE; (3x, 5 mm intervals) revealed a significant tachyphylaxis, however, in acidic skin the following plain pH stimulus was significantly more painful (by 61%, p<0 008, Wilcoxon test) than before PGE; injections

Conclusions' The other constituents of the combination of inflammatory mediators, bradykmm, histamme, serotonm, have recently been found, as single agents, to have a very limited influence on pH-mduced pain in the skin Thus, PGE; seems to account for much of the potentiation of experimental acidosis pain, which is so effectively blocked by topically applied aspirin-like drugs (Steen et al , Pain 62 (1995) 339-347, Pain 64 (1996) 71-82)

Acknowledgments This work was supported by the Deutsche Forschungsgememschaft, grant Ste 593 / 1-3

MONOMODAL SENSATIONS OF SKIN PAIN BROUTH ABOUT BY FOCUSED ULTRASOUND AND LASER RADIATION

Efim Tsirulnikov. Sechenov Inst of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, Saint-Petersburg, Russia

Aim of Investigation To test the possibilities of the focused ultrasound and laser radiation for the demonstration ofmonomoddl skin pain kinds not mixed with the other skin sensation existence

Methods Impulses with growing intensity of focused ultrasound (2MHz frequency, 50ms duration) and laser radiation (wave length of 446, 510, 578, 1064nm, duration 20-50ms) were directed on the glabrous skin of the palm and fingers to 6 healthy volunteers till having the skin pain Descriptions of the pain were recorded at the nearthreshold level

Results Monomodal skm pain appeared as some pin prick pain, burning pain, heat or hot pain and pure pain i e the pain after the short strong strike on a finger tip skin

Conclusions It is proposed that every kind of induced skin pain and every type of afferent nerve fibres are connected with each other The supposition might be verified in future by, for example, neurography and evoked brain potentials methods

Acknowledgments Supported in part by The Royal Society, UK

DETECTION THRESHOLD FOR FIRST PAIN BASED ON CONTINUOUS WAVELET TRANSFORM OF SINGLE TRIAL LASER EVOKED BRAIN POTENTIALS

Andre Mouraux*. Laurent Bairy*, Leon Plaghki, Faculty of Medicine, Universite catholique de Louvam, B-1200 Brussels, Belgium

Aim of Investigation To measure the threshold of first pain using a neurophysiological correlate of detection i e the wavelet transform of single trial late Laser Evoked brain Potentials (LEPs)

Methods CO; laser stimuli (50 ms duration, six different intensities in random order of equal probability, surface area 25 mm2, ISI 6-10 s, n=120/subject) were applied to the dorsum of the hand in 10 healthy subjects Perception intensity was measured on a 101 point VAS Reaction times (RTs) were obtained by instructing the subjects to press a button at the first sensation felt EEG was recorded from Cz vs linked earlobes along with EOG Present laser stimulation parameters generate a late N240-P390 complex maximum at the vertex in time averaged EEG records Continuous wavelet transforms were performed on single trial non-artefacted vertex potentials allowing computation of a volume by summing the voxels (Time x Scale x Coefficient) in a prestimulus (Vpre; ,time= -300-0 ms) and poststimulus (Vpost, time= 150-450) window Magnitude of the ratio Vpost/Vpre pennitted to predict the presence of a late-LEP

Results Probability of detection curves based on RTs or presence ofLEPs in single tnals were similar The thresholds for first pain were on average identical (8 1 0 9 mJ/mm2)

Conclusions Continuous wavelet transform performed on single tnals allows to identify the presence oflate-LEPs as evidence for sensory and cognitive processing of the stimulus and to compute the detection threshold for first pain with the same accuracy as conventional methods

THERMAL AND VIBRATORY PERCEPTION AND PAIN THRESHOLDS IN CHILDREN

Petra Meier*. Charles Berde, James DiCanzio*, David Zurakow-ski*, Navil Sethna, Depts of Anesthesia and Research Computing, Children's, Boston, MA 02115, USA and Dept of Anesthesia, Univ Hospital, 3010 Bern, Switzerland

Aim of Investigation (1) To charactenze pediatnc norms of thresholds for warm (WS) and cold (CS) sensations, heat (HP) and cold (CP) pain, and vibration (VS) (2) to compare method of limits (MLI) to levels (MLE), (3) to assess reproducibility

Methods. Consent/assent followed Institutional and IASP guidelines WS, CS, HP, CP & VS thresholds were measured on hands and feet and repeated after 3-6 weeks in 49 healthy children, 5-17 yrs,M/F 18/31

Results. Group variation for CS, WS, and VS was small, e g hand CS 25-75%tile was 30 3-31 0C Between-session group median differences for CS and WS were < 0 2C for hands and feet, using both MLI & MLE On the second session, there was greater tolerance of both CP and WP by a median of nearly 2 C in both directions No gender differences were seen (P=n s) HP varied less than CP HP vaned with age (p<0 01), CP did not

Conclusions. Children ages 5 and above can perform QST with precision and repeatability comparable to adults The greater tolerance of both heat and cold pain in a second session may reflect several factors, including learning and reduced anxiety MLE and MLI agree well, MLE is less biased These normative data may facilitate use of QST in study ofneuropathic pain in children

Acknowledgments NICHHD grant 1R01HD35737 & Bemische K-rebsliga, Braun AG, Smtetica SA, Dept Khnische Forschung der Unv Bern, SGAR Switzerland

MANIPULATION OF ATTENTION WITHIN THE SOMATOSENSORY SYSTEM

Francis McGlone'. Donna Lloyd*', Steven Tipper*2, 'Unilever Research, L633JW UK, School of Psychology, Univ of North Wales, Bangor, UK LL57 2DG

Aim of Investigation. To investigate the role of the a-delta pain system in somatosensory attention and its ability to interrupt current cognitive activity or basic orienting mechanisms such as Inhibition of Return (IOR)

Methods. Forty female subjects were bilaterally stimulated (thenar eminences) with a blunt probe dnven by two shakers A non-attended cue was randomly delivered to each site, proceeded at a fixed stimulus onset asynchrony (SOA) of 200 or 700 msec by a target to which the subjects responded, providing RT's via a foot-switch. Stimuli were either painful (50ms 8dB ramp indentation), or non-painful (5 cycle, 100 Hz sine wave) and occurred at the same or opposite spatial locations with a 50% probability Four conditions employed, tactile cue/tactile target, painful cue/tactile target, painful cue/painful target, tactile cue/painful target

Results. In all conditions IOR occurred robustly at the longer SOA's However, when the target was painful, RT was least inhibited compared with the touch/touch condition (p<0 02) The greatest reduction in inhibition was observed with the long SOA/comcident condition with a tactile cue/painful target Increases in RT are dependent upon target modality as the intensity of the cue produces no decrease in inhibition

Conclusion The pain system operates under the same reflexive orienting mechanisms as other sensory modalities and is subject to the same spatial selection of events in the environment

EPINEPHRINE-INDUCED HYPERALGESIA AND THE INFLUENCE OF ANXIETY ON PAIN

Sabme A. Janssen*. Amoud Amtz, Sabme Bouts* (SPON Dr Richel Lousberg), Dept of Clinical and Health Psychology, Leiden Univ, P 0 Box 9555, 2300 RB Leiden (first author), Dept of Experimental, Medical and Clinical Psychology, Maastricht Univ, P 0 Box 616, 6200 MD Maastricht, The Netherlands

Aim of Investigation Because of their possible role in the influence of an anxious state on the perception of pain, hyperalgesic effects of natural doses ofepmephnne in blood were investigated Methods Epmephnne and placebo were mtravenously infused in three increasing doses The effect ofepmephnne was measured within subjects on several subjective and autonomic measures subjective pain, skin conductance response and heart rate response due to electrical stimulation, threshold for heat pain, and threshold for pressure pain Heat pain threshold was measured both on normal skin and on skin sensitized with capsaicm, regarding indications that effects of sympathetic stimulation are only to be found in damaged or sensitized skin

Results Epmephnne caused a slight increase in subjective pain due to electrical stimulation, and a decrease in heat pain threshold, which was larger on capsaicm-treated than on normal skin However, heart rate response due to electrical stimulation and pressure pain threshold were not significantly influenced, while skin conductance response was even inhibited by epmephrme Furthermore, attentional focus, which was manipulated within electrical stimulation, appeared to have a much stronger influence on pain responses than pharmacological manipulation, independent ofepmephnne

Conclusions Evidence was found for pain-increasing effects of natural doses ofepmephnne, particularly on sensitized skin It is speculated that these hyperalgesic effects ofepmephnne could play a role in the influence of anxiety on pain, although they may be overruled by stronger effects of attentional focus

Acknowledgments This research was conducted while S A Jans-sen was supported by the Netherlands Organization for Scientific Research (NWO)

PARADOXICAL CHANGE OF THE CHEMOSENSITIVITY IN A SECONDARY ZONE OF CUTANEOUS HYPERALGESIA IN HUMANS

Lars Arendt-Nielsen, Gang Wu. Laboratory for Experimental Pain Research, Center for Sensory-Motor Interaction, Aalborg Univ, Aalborg, Denmark

Aim To examine the chemosensitivity in a secondary zone of cutaneous hyperalgesia following an experimental cutaneous injury (capsaicm application) in humans

Methods The skin was sensitised by topical application ofcapsai-cm in 17 volunteers Secondary hyperalgesia was mapped by punctuate mechanical stimuli Histamme was used to examine the chemosensitivity The intensity ofhistamme-mduced itch was rated on a visual analogue scale (VAS, 0-10) Responses ofchemosensi-tive C nociceptors to histamme were monitored by microneu-rographic recordings

Results Sensations of itch evoked by histamme, performed simultaneously on both arms, were compared in the same volunteer It was found that topical capsaicm produced clear secondary hyperalgesia to the mechanical stimuli. Itch intensity in the secondary hy-peralgesic area was significantly reduced compared with placebo. Seven mechanically insensitive C afferents were identified with the 'marking' technique. The results of the microneurographic recordings suggested that the sensitivity ofchemosensitive C nociceptors within the zone of secondary hyperalgesia might not deteriorate in the peripheral.

Conclusions: The skin chemosensitivity deteriorates within zones of secondary hyperalgesia probably via the central mechanisms in humans. Supported by the Danish National Research Foundation.

SECONDARY HYPERALGESIA TO PUNCTATE STIMULI IN HUMANS IS MEDIATED BY CAPSAICIN-INSENSITIVE A-FIBER NOCICEPTORS

W. Mageri'. P. N. Fuchs2, R.A. Meyer2-3, R.-D. Treede'. 'Inst of ; Physiology and Pathophysiology, Johannes-Gutenberg-Univ, Mainz, Germany, ^ept ofNeurosurgery, ^Applied Physics Lab., Johns Hopkins Univ, Baltimore MD, USA

Aim of Investigations: Pain and hyperalgesia to punctate mechanical stimuli are mediated by A-fiber nociceptors as shown by selective A-fiber conduction blockade (Ziegler et al., Pflugers Arch. 433 (1997) R32). We have now tried to identify, which subgroup(s) of A-fiber nociceptors mediate the hyperalgesia to punctate stimuli.

Methods: Stimulus response functions for pricking pain to punctate stimuli were determined with calibrated mechanical stimulators (200 urn 0, 8 - 512 mN). Capsaicin (40 ug) was intradermally injected to elicit secondary hyperalgesia. Pain and secondary hyperalgesia in normal skin with functionally intact innervation were compared to skin, where capsaicin-sensitive afferents were blocked by repeated topical treatment with 10% capsaicin cream (6 hrs./day for 2 days).

Results: Topical capsaicin induced near complete analgesia to heat (95 3% reduction of pain to radiant heat stimuli, p < 0.001). In contrast, topical capsaicin reduced pain to punctate stimuli only by 26% (p < 0.01). Pain was eliminated when capsaicin was combined with A-fiber block. After capsaicin injection, a similar magnitude of secondary hyperalgesia to punctate stimuli was observed in normal and capsaicin-treated skin.

Conclusions: Although capsaicin-sensitive afferents make a minor contribution to pricking pain, secondary hyperalgesia to punctate stimuli is mediated by capsaicin-insensitive A-fiber nociceptors, such as A5-HTM or type I AMH.

Acknowledgments: Supported by NATO grant CRG 95032540495 and NIH grant NS 14447

PUNCTATE SECONDARY HYPERALGESIA FOLLOWING A THERMAL INJURY IS MEDIATED BY C-FIBERS AND REVERSED BY COOLING AND LOCAL ANESTHETICS

Torhild Wamcke, Ellen Jorum. Dept. of Neurology, The National Hospital, Oslo, Norway.

Aim of Investigation: To study mechanisms of punctate secondary hyperalgesia.

Methods and Results: Hyperalgesia was induced by a local 1° bum (Somedics Thermotest, 47°C, 7 min) injury covering 12,5 cm 2 on the medial side of the calf in ten healthy volunteers. Cooling of the skin to a temperature of 10 C reversed punctate hyperalgesia in both primary and secondary area, separately. The hyperalgesia remained absent or reduced until skin temperatures reached 18 -24° C in the area of thermal injury and 22 - 24° C in the surrounding secondary area. Following ischemic block of thick myelinated A p- and thin myelinated A 5-fibers with the subsequent loss of sensation of touch and cold distal to the block, punctate hyperalgesia persisted, indicating conduction in thin unmyelinated C-fibers. Cooling of the skin in the secondary zone during effective nerve block eliminated punctate hyperalgesia indicating a peripheral effect on nociceptors in this area. Xylocain (10 mg/ml), 3 x 1 ml injected s.c. in part of the secondary area eliminated the punctate hyperalgesia in the area covered by the local anesthetics without eliminating the sense of touch.

Conclusions: the present study shows that punctate hyperalgesia is mediated by C-fibers. We find it difficult to explain the reversal of punctate hyperalgesia by cooling and xylocain by the theory of central sensitization altogether and raise the question as to whether peripheral sensitization mechanisms also may be involved.

VASCULAR AND SENSORY CHANGES IN THE SECONDARY HYPERALGESIC AREA FOLLOWING REPEATED HEAT CONDITIONING OF THE PRIMARY HYPERALGESIC AREA

Aysen Yucel. Akiko Miyazawa*, Ole K. Andersen, Lars Arendt-Nielsen, Laboratory for Experimental Pain, Center for Sensory Motor Interaction, Univ ofAalborg, DK-9200, Aalborg, Denmark.

Aim of Investigation: To investigate the vascular and sensory responses in the secondary hyperalgesic area following repetitive heat conditioning of the primary hyperalgesic area.

Methods: Thirteen volunteers (29.U2.33yr.) participated in the study. After baseline measurements of blood flow (BF), skin temperature (ST), and heat pain threshold (HPT), 1,5g. of capsaicin cream was applied on both forearms for 30 min. After removal of the cream, areas of touch allodynia, pinprick hyperalgesia and visible flare were measured. BF, ST and HPT were measured in primary and secondary hyperalgesic areas on both forearms. The ongoing pain evoked by capsaicin and conditioning stimulation (VAS 0-1 Ocm.) were rated for both arms. All measurements were repeated after heat conditioning of the primary hyperalgesic area on one arm using 35.5-40C for 2 min. The heat conditioning was repeated three times separated by 30 min. Repeated measure ANOVA was used for statistical analysis.

Results: Mean pain score was 6.12.6 after the capsaicin application. After the first heat conditioning, the ongoing pain was lower on the heated arm (1.92.6 vs 3.42.3, p<0.05). The ST and BF within the primary and secondary hyperalgesic area were elevated after the removal of the cream on both arms. There were no effects of heat conditioning on ST and BF values. The area of visible flare was slightly increased after the first heat conditioning on the heated arm. There was no effect of heat conditioning on areas of touch allodynia and pinprick hyperalgesia.

Conclusions: Repetitive heat conditioning had no effect on the secondary hyperalgesic area regarding blood flow, skin temperature and sensory tests.

Acknowledgment: Supported by the Danish National Research Foundation.

THE EFFECTS OF SUBCUTANEOUS ADMINISTERED LIDOCAINE AND KETAMINE ON SECONDARY HYPERALGESIA INDUCED BY INTRADERMAL CAP-SAICIN IN HEALTHY VOLUNTEERS

Hanne Gottrup'2, Flemming Winther Bach', Lars Arendt-Nielsen3, Troels Staehelin Jensen12, Dept. of Neurology', Danish Pain Research Center2, Aarhus Univ Hospital, DK-8000 Aarhus C, Lab. of Experimental Pain Research, Aalborg Univ, DK-9220 Aalborg3, Denmark

Aim of Investigation This study examined the effect ofpre-inJury subcutaneous treatment with the NMDA antagonist ketammc, the sodium blocker lidocame or saline on pain and hyperalgesia induced by intradermal capsdicin

Methods' 12 volunteers participated in each experiment, which was a randomised, double blind, placebo-controlled, crossover study Experiment 1 Each subject received 100 ng of capsaicin mtrader-mally on the volar forearm 10 mm after prc-treatment of the injection side with 20 mg lidocame or saline Experiment 2 Subject was pre-treated in a similar fashion but with 5 mg ketamme or saline Volume injected was 2.0 ml in each expenment The active drug was injected on the contralateral arm if saline was injected at the capsaicin site and vice versa. Spontaneous pain, evoked pain (brush, punctate) and areas of punctate and brush-evoked hyperalgesia were measured.

Results Lidocame reduced spontaneous pain (p<0 001), pain evoked by brush and punctate stimuli (p<0.001) and the areas of brush-evoked and punctate-evoked hyperalgesia (p<0 001) Keta-mme had no effect on spontaneous pain, evoked pain or the areas of secondary hyperalgesia Punctate-evoked pain and the area of punctate hyperalgesia were less when ketamme than lidocame was given in the opposite arm, but not significantly Lidocame produced no side effects while ketamme in 6/24 (25%) gave rise to side effects (paresthesia, dizziness, and sleepmess)

Conclusion A reduction of the afferent C-fiber input by a sodium channel blocker reduced hyperalgesia induced by intradermal cap-saicm. Peripheral NMDA receptors do not play any significant role in hyperalgesia induced by capsaicin A systemic effect ofketa-mme is likely when injected subcutaneous.

AGE-RELATED DIFFERENCE IN THE TIME COURSE OF CAPSAICIN-INDUCED PUNCTATE HYPERALGESIA IN HUMANS

Zhen Zheng. Stephen J Gibson, Robert D Heime, Joan M McMeeken*, National Ageing Research Inst, PO Box 31, Parkville, Vie 3052, Australia, * School of Physiotherapy, Univ of Melbourne

Aims of Investigation. To investigate the age effect on the time course of heat and mechanical hyperalgesia induced by capsaicin

Methods. 0.1 ml of capsaicin with a concentration of 5mg/ml was applied topically on the forearm of 8 young (28 0 6 5yrs) and 8 elderly (78 8.8yrs) healthy volunteers for one hour In the following 10 hours, the intensity of pain response to capsaicin and the areas of flare, heat and punctate hyperalgesia (methods see La-Motte et al (1992) were measured repeatedly at one or two hour intervals

Results: Punctate hyperalgesia lasted for 9-11 hours in the two age groups. However, there was a significant age effect on the time course (p = .020). In the elderly, punctate hyperalgesia did not resolve until 5 hours after the application of capsaicin, while, in the young, it resolved as soon as the capsaicin patch was taken off No age effects were detected on either the magnitude or the time course of heat hyperalgesia, flare, and capsaicin pain The latency of the first pain response to capsaicin or of the maximal pain was not significantly different in the two age groups.

Conclusions Following an acute injury, the elderly have a similar degree of response compared with the young However, their punctate hyperalgesia is maintained for a longer time, perhaps indicating a poorer adaptation of the central nervous system to inflammation with increased age.

PSYCHOLOGICAL MODULATION OF A NOCICEPTIVE WITHDRAWAL REFLEX IN HUMANS

A J Terkelscn'. T.S Jensen1, 0 K. Andersen2, P.O. Hansen', L. Arendt-Nielsen2, 'Dept of Neurology and Danish Pain Research Center, Univ Hospital of Aarhus, DK-8000 center for Sensory Motor Interaction, Univ of Aalborg, DK-9220

Aim of Investigation To investigate the effect of attention to and distraction from sural nerve stimulation on the Nociceptive Withdrawal Reflex (NWR) and VAS-score of sural nerve stimulation.

Material and Methods Thirteen healthy male volunteers were included Mean age 24 9 years Range 21-28 years Sural nerve stimulation Each stimulus consisted of a standard pulse tram of 21 ms duration consisting of five unipolar rectangular 1 ms pulses The intensity was 20 percent higher than the reflex threshold and randomly delivered every 15 sec (13 -17 sec.) Recording of EMG-responses Recording electrodes were placed on the skin above the short head of the biceps femons muscle ipsi-lateral to nerve stimulation.

Conditioning stimuli Test 1 Distraction from sural nerve stimulation by adding pairs of digits Test 2' Attention to sural nerve stimulation by counting the number of nerve stimuli

Results' Distraction from sural nerve stimulation significantly inhibited the VAS-score of sural nerve stimulation with 19% before and 17% after a 30-mm pause (p < 0 05) Distraction from sural nerve stimulation significantly inhibited the NWR with 18% before pause but was without any inhibitory effect after pause (p < 0 05). Attention to sural nerve stimulation significantly inhibited the NWR with 13% and VAS-score with 6% before a 30-mm pause but was without any inhibitory effect after pause (p < 0 05)

Conclusion. Attention to and distraction from sural nerve stimulation induce inhibition of the NWR and VAS-score of sural nerve stimulation The variable inhibitory effects propose involvement of different mechanisms

SPATIAL SUMMATION OF PAIN PROCESSING IN THE BRAIN: HEAT EVOKED POTENTIALS IN MAN

David Niddam. Helen Crawford*, Jesper Nielsen, Lars Arendt-Nielsen, Andrew CN Chen, HBMCI Laboratory, SMI, Aalborg Univ, DK-9220, Denmark *visitmg scientist from Virginia Polytechnic Inst. & State Univ USA.

Aim- To investigate the cerebral evoked responses to non-painful and painful stimulation of contact heat electrodes comparing one \s two spots for understanding the cortical representation of spatial summation in pain processing

Methods. Thirteen normal male subjects (age. 25 54 1) participated in the study Contact heat stimulus (Intensity 2, 4, 6, corresponding to the individual's non-pain, slight pain, and moderate pain) was delivered singly or in pairs via Peltier electrodes (20mm diameter, 6mm separation) on the ventral portion of fore-arm EEC signals were recorded (31 ch ear-reference, 256 Hz sampling, 0 1-100 Hz bandpass) Grand mean waveforms were obtained at each intensity level T-tests were conducted for statistical analyses

Results. In psychophysics, systematic effects between stimulus intensities and heat spots were observed In heat EPs, the prominent activation resided at vertex and vicinity The significant spatial summation effects were shown only in the intensity of pain levels, but not the non-pain intensity For the moderate pain level, the main effect was a significant latency shift between one-spot and two-spot (297 7 vs 254.7ms, p<02) and an increase of amplitude (-144 vs -17.0uV,p<04)

Conclusion Central pain processing in heat-EPs clearly reflects the perceptual effects of spatial summation Understanding of brain function is essential for integration of bodily sensations

Acknowledgment Supported by the Danish National Research Foundation

SPATIAL SUMMATION OF HEAT PAIN IN MALES AND FEMALES

StefanLautenbacher'. Jesper Nielsen2, Thim Andersen2', Lars Arendt-Nielsen2', 'Dept of Psychiatry and Psychotherapy, Univ of Marburg, Germany, center for Sensory-Motor Interaction, Univ of Aalborg, Denmark

Aim of Investigation Spatial summation of pain depends on the density ofnociceptive fibers and the degree of central neuronal convergence There might be a relationship between these factors and body size which could result in sex differences in spatial pain summation andvia this mechanismto pain perception in general Hence, we investigated sex differences in spatial summation of heat pain in healthy volunteers

Methods Twenty women and 20 men of similar age and body mass index took part in the study Pain thresholds were assessed by a tracking procedure and supra-threshold pain perception by numerical ratings of stimuli individually tailored tabe above pain threshold Heat stimuli were administered by thermodes with contact areas of 1 cm2, 3 cm2, 6 cm2 and 10 cm

Results' Pain thresholds were significantly higher with smaller areas stimulated than with larger ones No comparable effect was found for the ratings of the supra-threshold stimuli In neither of the two parameters were there any sex differences

Conclusions Spatial summation of heat pain appeared to result mainly in a shift of pain threshold No further summation effect was found for supra-threshold stimuli individually tailored to be above pain threshold Sex differences did not occur with any of the different contact areas used suggesting no sex differences in spatial pain summation The complete lack of sex differences in heat pain perception in the present study contributes to the controversy regarding sex differences in pain perception to heat stimuli

HYPERALGESIA IN OUTPATIENTS WITH DERMAL INJURY: QUANTITATIVE SENSORY TESTING VERSUS A NOVEL SIMPLE TECHNIQUE

Carr DB. Wnght C, Goudas LC, Bentch A, Perry PP, Depts of Anesthesia & Pharmacology, Tufts-New England Medical Center, Boston MA and Uniformed Services Univ of the Health Sciences, Bethesda MD USA

Aim of Investigation To quantitate tactile and thermal hyperalge-sia in outpatients with dermal injury using standard methods and two novel, simple assessment devices

Methods After IRB approval, 40 evaluable subjects were enrolled All had acute thermal, chemical, mechanical or infectious skin injury Subjects were tested (0-100 mmVAS) at the injured site, the "mirror" site, and a nonmjured ipsilateral control site Quantitative thermal sensory testing (MEDOC) was followed by 5-second applications (random sequence) of copper rods preheated to 40, 43, 46 and 49 C (CLINTHERM, Adolor) Pressure testing was conducted with a 1 5 inch diameter gauge

Results: Rest pain was 22 1 3 87 (SEM) Expected pain on touch was 50.7 4 44 (p<0 001 vs rest) and on application of heat or cold was 44 4 4 45 (p<0 001 vs rest) Thermal discomfort threshold was 47 5C 0 66 (control site), at the mirror site it was 46 4 0 50 (p<0 05 vs control) and at the injured site 40 7 0 66 (p<0 001 vs control) Pressure discomfort thresholds followed a similar pattern All 4 challenge temperatures elicited VAS scores markedly greater at injured than at mirror or control sites (p<0 001 vs control)

Conclusions Hyperalgesia (manifest as increased perception of pain to threshold stimuli) is common in routine dermal injury Quantitation of contribution of thermal and tactile hyperalgesia, and assessment of the antihyperalgesic effects of pain therapy, is feasible using simple, rugged, low-tech, low-cost methods Inter-subject variation was remarkably low

Acknowledgments Adolor Corp and the Saltonstall Trust

AUGMENTATION OF PAIN RESPONSE IN DYSMENORRHEA: A SUPRA-THRESHOLD PSYCHOPHYSICAL STUDY

Michal Granof'. Ethan Zimmer*, Elliot Sprecher, David Yamitsky, Depts of Neurology and Gynecology, and Haifa Pain Research Group, Rambam Medical Center, Technion Medical School, Haifa, Israel

Aim of Study Dysmenorrhea affects up to 20% of young women, causing loss of quality of life It is unclear whether pain is exclusively ofutenne on gin, or is attributable to central factors as well We sought to determine whether central augmentation of pain perception might be implicated

Methods 24 dysmenorrheic and 22 age-matched control women were studied at 4 times during the menstrual cycle In each session, we determined heat-induced pain thresholds at the hand, then administered repeated, randomized stimuli at 1 5, 3 0 and 4 5C supra-threshold Subjects estimated pain magnitude by 100 point Visual Analog Scale (VAS) Dysmenorrhea, menstrual cycle, and interaction effects were investigated by log-transformed regression, to derive parameters of Stevens' psychophysical law, P=k(I-Io)s, where P = percept estimate (VAS), k = scaling unit factor, 1 = (thermal) stimulus, Io = (thermal) threshold, and S = characteristic sensory exponent

Results Both groups evidenced similar pain thresholds (dysmenorrheic women 42 0C vs. controls 41 4C) Supra-threshold analysis indicated no group difference in S (=0 57), and no menstrual cycle effect However, k was significantly higher (p=0 002) for dysmenorrheic subjects versus controls, with psychophysical equations P = 35.7(I-Io)57 and P = 24.6(I-Io)57 respectively This reflects consistently higher pain scaling by dysmenorrheic women

Conclusion' Dysmenorrheic women had an augmented perception of pain, as revealed by the supra-threshold stimuli Supra-threshold stimuli are thus critical for a complete psychophysical assessment of pain responsiveness Augmented response to external pain stimuli at a non-genital site suggests central neural pain processing is important in pathogenesis of dysmenorrhea

ALLODYNIA AND PSYCHOLOGICAL PROFILE IN CHRONIC WHIPLASH PATIENTS

M Moog, M Zusman, J Qumtner, and T Hall*, School of Physiotherapy, Curtm Univ of Technology, Shenton Park WA 6008 Australia

Aim of Investigation: To elucidate mechanisms of chronic pain and allodyma following whiplash injuries Methods 43 whiplash patients with chronic neck pain were compared to 43 healthy control subjects Neck Disability Index (NDI), McGill Pain Questionnaire (MPQ), and the Symptom Check List-90-R (SCL-90-R) were administered to both groups A vi-brameter with adjustable frequency (10-lOOhz) and amplitude (0-2 5mm) was used to stimulate (in an ascendmg/ descending manner) 6 test sites, within and outside areas of pain, whilst sensory threshold, any change to present pain status, and intolerance were recorded.

Results 28 patients consistently reported pain on vibration (VP) No significant differences in sensory threshold were noted between patients and controls (none of whom exhibited VP) SCL-90-R profiles showed an overall elevated level of distress in the patients compared to controls In those with VP, elevated disability scores correlated with higher pain intensity and the number of affective pain descriptors used on MPQ Complaints of arm pain and/or paraesthesiae soon after the accident had a high predictive value for both VP and chronic disability

Conclusions Pain felt on vibration over presumably healthy tissues in 65% of the whiplash patients suggests a contribution of central nervous system mechanisms (sensitization) to the clinical picture Severe arm pain and paraesthesiae soon after injury both appear to be predictors ofVP and chronic disability Psychological factors may contribute to the development and maintenance of chronic pain and disability

MEASURES OF TACTILE SENSIBILITY ON THE ANTERIOR THORAX OF NORMAL ADULTS AND ADULTS HAVING EXPERIENCED A SPINAL CORD LESION

Fatima Saddiki-Traki, Nicole Tremblay, Robert W. Dykes and A El-Khamlichi Faculte des Sciences et de medecme, Univ Mo-hamed V Rabat, Maroc et Facultes des sciences infirmieres et de medecme, Univ de Montreal, Quebec, Canada.

The tactile sensitivity of 9 spmal-cord-mjured patients was evaluated on the thorax above the anesthetic region using psycho-physical methods at test sites separated by 3 cm The threshold of touch was measured using Semmes-Wemstem monofilamcnts and the method of limits Magnitude estimations were performed with three different-caliber brushes.

In 13 control subjects, the threshold for touch was uniform across the tested sites and unaffected by age or sex, but was higher than values reported in the literature for stimulus sites on the forearm or the forehead For the 9 patients, the monofilaments were difficult to detect near (0-12 cm) the anesthetized region and the detection threshold was elevated in comparison to test sites farther rostral. Outside of this transition zone, the touch threshold decreased to a value that was constant or the rest of the anterior thorax, but was still 45% higher than thresholds in the controls

In control subjects, the ability to estimate the three stimulus intensities remained constant across the trunk In patients, the reported intensity increased with increasing distance from the anesthetized region for the first 12 cm Beyond the boundary zone, the estimates were 62% greater than control subjects

The raised threshold confines the patient to a narrow range of sensory experiences, but once activated, the sensory pathway provides a large and clear signal to the central perceptual processes, forcing the patient to make estimates within a reduced dynamic range of possible sensory experiences Acknowledgments Supported in part by Canadian MRC Grant to RWD and FRSQ to NT.

TEMPORAL SUMMATION AND REDUCTION OF PAIN THRESHOLDS IN NORMAL SKIN IN PATIENTS WITH DYSESTHETIC CENTRAL PAIN FOLLOWING SPINAL CORD INJURY

Christine N. Sang. Victoria A Miller*, Lanssa Dobosh*, Richard H Gracely, Douglas Hayden* Dept of Anesthesia, Massachusetts General Hospital, Boston, MA 02114, USA

Aim of Investigation To evaluate the extent and mechanisms of spontaneous and evoked dysesthetic pain in 41 patients with SCI

Methods: Areas of spontaneous mechanical allodynia (2x2 gauze) and pinpnck hyperalgesia were quantified and sensory testing was performed at both forehead (control) and affected sites (of allodynia, if present, or 3 levels below sensory level) Constant current electrical stimuli (2 ms pulses at 0 5 and 200 Hz) were used to determine pain at detection (PAD) defined as a pain/detection threshold ratio $ 2 0 A 3x3 cm2 thermode assessed heat hyperalgesia (heat pain at warm detection threshold,) and cold allodynia (cold pain at ^ 20C).

Results Patients were categorized as complete (no sensory/motor function at lowest sacral levels, 46%) or incomplete (54%) and by level of injury (cervical (44%), thoracic (44%), lumbar (12%)) 83% had allodynia (of this group, 68% were segmentally distributed, 15% involved the entire body including parts of the face). In the affected areas, presence of cold allodynia (p=0 006), heat hyperalgesia (p=0 031), electrical PAD at 0 5 Hz (p=0 003), and mechanical allodynia (p=0 035) predicted presence of cold allodynia in the forehead In patients with allodynia, electrical PAD (200 Hz trains) was observed on the forehead in 44%, which was predicted (p=0.03) by the presence of PAD with 200 Hz trains applied to the affected area. Neither ASIA classification nor site of injury predicted sensory abnormalities in the forehead

Conclusions Our findings suggest that SCI results in sensitization of central neurons which accounts for cephalad spread of cold allodynia and of augmented temporal summation evaluated by electrical PAD

Acknowledgments Supported by the Paralyzed Veterans of America Grant # 1752

9th WORLD CONGRESS ON PAIN, 1999, Vienna, Austria, p.405 - 410

   

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