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Antinociceptive circuitry associated with TMJ inflammation
S18 (637) Antinociceptive circuitry associated with TMJ inflammation P. Thut, A. Davoody, T. Hermanstyne, M. Gold; University of Maryland Dental School, Baltimore, MD Temporo-Mandibular Disorder (TMD) is debilitating syndrome often associated with severe pain that limits oro-motor function. Because TMD often resolves on its own, even in the absence of clinical intervention, it is of interest to determine factors that underlie both the onset and recovery of TMD. The present study was designed to address the latter. Previous studies in the laboratory suggested that persistent temporomandibular joint (TMJ) inflammation in the rat results in alterations in feeding behavior that normalized in the face of persistent inflammation. Thus, we have tested the hypothesis that the decrease in nociceptive behavior associated with prolonged TMJ inflammation reflects the activation of opioid dependent antinociceptive circuitry. A conditioning paradigm was used to assess feeding behavior in rats where the time between food rewards (inter-feeding-interval (IFI)) was used as the dependent variable. Persistent inflammation was induced with an injection Complete Freud’s Adjuvant (CFA) into the TMJ. 24h after CFA injection the median IFI increased from a baseline of 34.3 ⫾ 1.7 to 46.1 ⫾ 3.6 (n⫽10) seconds. By 72 h, the median IFI returned to baseline. Naloxone, given IP 10 minutes before testing in a second group of rats at 72h rekindled the feeding deficit to 90 ⫾ 13% of that observed at 24h. A third group of rats received an IP injection of naloxone-methiodide, an opioid receptor antagonist that does not cross the blood brain barrier, at 72h and this failed to rekindle the feeding deficit. Neither naloxone nor nalaxone-methiodide had any effect on feeding behavior in uninflamed rats. Our results suggest that recovery of pain associated with TMJ inflammation reflects the activation of an opioid dependant antinociceptive circuit within the central nervous system. Importantly, our results also suggest that patients suffering from persistent TMD pain may suffer because of a deficit in their endogenous pain control circuitry.
B08 - Human Pain Models: Other (638) Effect of chronic oral gabapentin on capsaicin induced allodynia and hyperalgesia: A double-blind, placebocontrolled, crossover study M. Wallace, G. Schulteis; University of California San Diego, San Diego, CA There is an abundance of literature on the efficacy of gabapentin for the treatment of neuropathic pain. Two studies have demonstrated an effect of a single dose of oral gabapentin on experimental cutaneous hyperalgesia. This study evaluated the effect of the chronic delivery of oral gabapentin on experimentally induced cutaneous hyperalgesia. A randomized, double-blinded, placebo controlled crossover design methodology was conducted. Subjects participated in two, 10-day study sessions, separated by a 7-day washout period. One session was with gabapentin and one with placebo. Study drug was administered 300mg BID from days 1-3, 300mg QID from days 4-6 and 600 mg TID from days 7-10. At baseline, day 4, day 7, and day 10, quantitative sensory testing was performed to thermal and mechanical stimuli. On day 10 only, intradermal capsaicin was injected on the volar aspect of the forearm followed by an assessment of pain and hyperalgesia. Side effects were recorded by the subjects each evening. Thirteen subjects were enrolled into the study. Three dropped out because of intolerable side effects. Ten subjects completed the study and were able to tolerate the highest dose of gabapentin. Oral gabapentin had no significant effect on acute sensory thresholds, pain, secondary hyperalgesia, or flare response induced by intradermal capsaicin. There were significantly more side effects associated with gabapentin with sedation and dizziness being the most common. This study demonstrated a lack of effect of the chronic delivery of oral gabapentin on experimentally induced cutaneous hyperalgesia. The discrepancy of this finding with other studies using single oral doses may be the result of differences in the models used and differences in drug kinetics and plasma levels. The results of this study do not correlate with the clinical studies on gabapentin which use higher doses (up to 3600mg/day).
Abstracts (639) Familial pain modeling and facial pain expressions A. Hsieh, T. Wang, K. Craig, D. Tripp; The University of British Columbia, Vancouver, BC Exposure to social models who exhibit intolerant or tolerant response to pain has been shown to have an effect on both reports of pain experience and behaviour. Patrick et al. (1986) reported that exposure to social models varying in pain tolerance during experimental pain affected both non-verbal display and self-report, but the impact was significantly greater on self-report than on facial expression. This discrepancy suggests social influences may be relatively slow to change facial expression of pain; however, modeling in the familial context may provide longterm pressure that can shape both verbal and nonverbal reaction to pain (Craig et al., 2001). To date, several studies have investigated familial pain modeling and pain experience using self-report measures (e.g. Fillingim et al, 2000), but the impact of family pain models on facial expression of pain has not been examined. We examined the relationship between familial pain models and both self-report of pain and facial expression of pain. We hypothesized that exposure to excessive pain through family history would be associated with atypical self-report and facial displays of pain. The study reports on 64 female undergraduate students who undertook the cold pressor (CP) task with a female observer present in the room. Participant’s facial expressions were videotaped through a one-way mirror. Participants provided family pain history prior to the CP task, pain unpleasantness (Verbal Rating Scale) during the task, and pain intensity (Visual Analogue Scale) after the task. Facial expressions were coded utilizing the Facial Action Coding System. Multiple regression analyses indicated family models significantly predicted CP time, F(1, 63)⫽5.294, p ⬍ .025, but not VAS, VRS and FACS score. Familial modeling seems to have more influence on nonverbal display than verbal report of pain. Further analyses will examine the impact of types and severity of pain on verbal and nonverbal pain behaviour.
(640) Heart rate mediation of sex differences in experimental pain in children Q. Lu, J. Tsao, L. Zeltzer, S. Kim, T. Norman, C. Myers, B. Naliboff; David Geffen School of Medicine at UCLA, Department of Pediatrics, Pediatrics Pain Program, Los Angeles, CA Converging evidence from multiple lines of research points to the existence of important sex and developmental differences in pain. However, the mechanisms underpinning such differences are not well understood. The aim of this study is to examine the relationship between sex and pubertal differences in pain tolerance and autonomic arousal to laboratory pain stimuli in healthy children. We tested the following specific hypotheses. 1) Early puberty children would have lower pain tolerance than late puberty. 2) Female children would have less pain tolerance than males, and 3) Sex and puberty differences may be associated with similar differences in autonomic arousal. Participants were 244 healthy children (51% female, mean age 12.73 ⫾ 3 yrs, range 8⬃18 yrs). Separate four trial blocks of cutaneous pressure and thermal pain stimuli were presented. Heart rate (HR) was recorded before, after and during trials. Overall, early puberty children had less pain tolerance than late puberty children in both cutaneous pressure (p⬍0.001) and thermal pain trials (p⬍0.0001). Early puberty children also had greater HR than late puberty children (p⬍0.001). Results also indicated decreased tolerance in female subjects for cutaneous pressure but not thermal pain (p⬍.05; mean tolerance females⫽32.98 ⫾ 3.96 sec; males ⫽45.26 ⫾ 3.97sec) and greater HR for female subjects both before and during the pain tasks (p⬍0.01, overall mean HR females⫽79.76 ⫾ 0.98; for males ⫽75.76 ⫾ 0.95). Mediation analysis showed that sex differences in pressure pain tolerance could be accounted for by sex differences in HR, although no evidence supported HR mediation of pubertal differences in pain tolerance. These results support that females and younger children generally demonstrate less pain tolerance and increased arousal as indexed by HR. HR may be a potential mediator of sex-related differences in pain responses in children. Supported by NIH/ RO1 DE12751-01A1.
B08 - Human Pain Models: Other (638) Effect of chronic oral gabapentin on capsaicin induced allodynia and hyperalgesia: A double-blind, placebocontrolled, crossover study M. Wallace, G. Schulteis; University of California San Diego, San Diego, CA There is an abundance of literature on the efficacy of gabapentin for the treatment of neuropathic pain. Two studies have demonstrated an effect of a single dose of oral gabapentin on experimental cutaneous hyperalgesia. This study evaluated the effect of the chronic delivery of oral gabapentin on experimentally induced cutaneous hyperalgesia. A randomized, double-blinded, placebo controlled crossover design methodology was conducted. Subjects participated in two, 10-day study sessions, separated by a 7-day washout period. One session was with gabapentin and one with placebo. Study drug was administered 300mg BID from days 1-3, 300mg QID from days 4-6 and 600 mg TID from days 7-10. At baseline, day 4, day 7, and day 10, quantitative sensory testing was performed to thermal and mechanical stimuli. On day 10 only, intradermal capsaicin was injected on the volar aspect of the forearm followed by an assessment of pain and hyperalgesia. Side effects were recorded by the subjects each evening. Thirteen subjects were enrolled into the study. Three dropped out because of intolerable side effects. Ten subjects completed the study and were able to tolerate the highest dose of gabapentin. Oral gabapentin had no significant effect on acute sensory thresholds, pain, secondary hyperalgesia, or flare response induced by intradermal capsaicin. There were significantly more side effects associated with gabapentin with sedation and dizziness being the most common. This study demonstrated a lack of effect of the chronic delivery of oral gabapentin on experimentally induced cutaneous hyperalgesia. The discrepancy of this finding with other studies using single oral doses may be the result of differences in the models used and differences in drug kinetics and plasma levels. The results of this study do not correlate with the clinical studies on gabapentin which use higher doses (up to 3600mg/day).
Abstracts (639) Familial pain modeling and facial pain expressions A. Hsieh, T. Wang, K. Craig, D. Tripp; The University of British Columbia, Vancouver, BC Exposure to social models who exhibit intolerant or tolerant response to pain has been shown to have an effect on both reports of pain experience and behaviour. Patrick et al. (1986) reported that exposure to social models varying in pain tolerance during experimental pain affected both non-verbal display and self-report, but the impact was significantly greater on self-report than on facial expression. This discrepancy suggests social influences may be relatively slow to change facial expression of pain; however, modeling in the familial context may provide longterm pressure that can shape both verbal and nonverbal reaction to pain (Craig et al., 2001). To date, several studies have investigated familial pain modeling and pain experience using self-report measures (e.g. Fillingim et al, 2000), but the impact of family pain models on facial expression of pain has not been examined. We examined the relationship between familial pain models and both self-report of pain and facial expression of pain. We hypothesized that exposure to excessive pain through family history would be associated with atypical self-report and facial displays of pain. The study reports on 64 female undergraduate students who undertook the cold pressor (CP) task with a female observer present in the room. Participant’s facial expressions were videotaped through a one-way mirror. Participants provided family pain history prior to the CP task, pain unpleasantness (Verbal Rating Scale) during the task, and pain intensity (Visual Analogue Scale) after the task. Facial expressions were coded utilizing the Facial Action Coding System. Multiple regression analyses indicated family models significantly predicted CP time, F(1, 63)⫽5.294, p ⬍ .025, but not VAS, VRS and FACS score. Familial modeling seems to have more influence on nonverbal display than verbal report of pain. Further analyses will examine the impact of types and severity of pain on verbal and nonverbal pain behaviour.
(640) Heart rate mediation of sex differences in experimental pain in children Q. Lu, J. Tsao, L. Zeltzer, S. Kim, T. Norman, C. Myers, B. Naliboff; David Geffen School of Medicine at UCLA, Department of Pediatrics, Pediatrics Pain Program, Los Angeles, CA Converging evidence from multiple lines of research points to the existence of important sex and developmental differences in pain. However, the mechanisms underpinning such differences are not well understood. The aim of this study is to examine the relationship between sex and pubertal differences in pain tolerance and autonomic arousal to laboratory pain stimuli in healthy children. We tested the following specific hypotheses. 1) Early puberty children would have lower pain tolerance than late puberty. 2) Female children would have less pain tolerance than males, and 3) Sex and puberty differences may be associated with similar differences in autonomic arousal. Participants were 244 healthy children (51% female, mean age 12.73 ⫾ 3 yrs, range 8⬃18 yrs). Separate four trial blocks of cutaneous pressure and thermal pain stimuli were presented. Heart rate (HR) was recorded before, after and during trials. Overall, early puberty children had less pain tolerance than late puberty children in both cutaneous pressure (p⬍0.001) and thermal pain trials (p⬍0.0001). Early puberty children also had greater HR than late puberty children (p⬍0.001). Results also indicated decreased tolerance in female subjects for cutaneous pressure but not thermal pain (p⬍.05; mean tolerance females⫽32.98 ⫾ 3.96 sec; males ⫽45.26 ⫾ 3.97sec) and greater HR for female subjects both before and during the pain tasks (p⬍0.01, overall mean HR females⫽79.76 ⫾ 0.98; for males ⫽75.76 ⫾ 0.95). Mediation analysis showed that sex differences in pressure pain tolerance could be accounted for by sex differences in HR, although no evidence supported HR mediation of pubertal differences in pain tolerance. These results support that females and younger children generally demonstrate less pain tolerance and increased arousal as indexed by HR. HR may be a potential mediator of sex-related differences in pain responses in children. Supported by NIH/ RO1 DE12751-01A1.