The journal of pain : official journal of the American Pain Society
-
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen by gastroenterologists. We discuss some recent evidence for potential neural mechanisms that could contribute to somatic and visceral hyperalgesia in IBS patients. The combination of research studies of human IBS patients and studies of rats with delayed rectal hypersensitivity after recovery from experimentally induced neonatal colitis strongly suggests a mechanism wherein both primary visceral hyperalgesia and secondary widespread cutaneous hyperalgesia are dynamically maintained by tonic impulse input from the noninflamed colon and/or rectum. The secondary hyperalgesia is likely to be at least partly related to sensitization of spinal cord dorsal horn neurons and in this respect might be similar to other persistent pain conditions such as fibromyalgia and complex regional pain syndrome. ⋯ Pain in irritable bowel syndrome is likely to be at least partly maintained by peripheral impulse input from the colon/rectum and central sensitization, yet it is also highly modifiable by psychological factors such as nocebo and placebo effects. A synergistic interaction might occur between psychological factors and abnormal afferent processing.
-
Randomized Controlled Trial
CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model.
CHF3381 is a new low-affinity, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and reversible monoamine oxidase-A (MAO-A) inhibitor. The analgesic activity of CHF3381 was investigated in the heat-capsaicin human pain model and compared with those of gabapentin. Twenty-seven young, healthy male volunteers received a single oral dose of CHF3381 (500 mg), gabapentin (1,200 mg), or placebo in a randomized, double-blind, crossover study design. Measurements were done before and 135 to 145 minutes after treatment administration and included area of secondary hyperalgesia around the sensitized skin of the forearm (45 degrees C for 5 minutes followed by topical capsaicin for 30 minutes), area of secondary hyperalgesia after thermal sensitization of the thigh (45 degrees C for 3 minutes), heat pain detection thresholds (degrees C), and pain on a visual analogue scale after long thermal stimulation (45 degrees C for 1 minute). Compared with placebo, both gabapentin and CHF3381 significantly reduced the area of secondary hyperalgesia on the dominant forearm. Median (and interquartile range) percent values over baseline were 86% after placebo (69% to 100%), 56% (41% to 76%) after gabapentin (P < .001), and 67% (49% to 88%) after CHF3381 (P < .009). Both drugs also significantly decreased the area of secondary hyperalgesia on the dominant thigh. The other pain variables were not significantly affected. Adverse events, mainly fatigue and dizziness, were mild to moderate. ⋯ This article presents the antihyperalgesic effect of CHF3381, a new NMDA receptor antagonist and reversible MAO-A inhibitor, in a human pain model and might guide the proper selection of CHF3381 doses to be used in Phase 2 studies in patients with neuropathic pain.
-
Temporal summation of second pain or windup (WU(SP)) can be reliably evoked in normal human subjects by repetitive heat pulses to the skin at frequencies of 0.33 Hz or more. This phenomenon is dependent on activation of peripheral C-nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C-fiber-evoked discharges of dorsal horn neurons. Several investigations of heat pain summation have used Peltier devices for intermittent-contact heat pulses to the skin. This method returns the skin to an adapting temperature between each stimulus and can result in distinct first and second pain sensations. An alternative method of temporal summation consists of continuous-contact heat stimuli by computerized Peltier thermodes that can provide rapid heat pulses. Previously used continuous-contact heat pulse trains, however, seemed to lack characteristics that result in efficient WU(SP). The present study sought to obtain psychophysical evidence that reliable WU(SP) can be elicited with an advanced pulse design by using a computerized heat-foil/Peltier thermode. WU(SP) was elicited by repetitive thermal stimulation of the hands at frequencies of 0.33 Hz but not 0.25 and 0.17 Hz. WU(SP) stimuli were either adjusted to resemble the heat transfer characteristics of intermittent-contact stimulus trains, or they remained unadjusted. The estimated transmission velocity of impulses giving rise to second pain and WU(SP) was characteristic of C fibers. More pronounced second pain and efficient WU(SP) could be elicited with adjusted than with unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU(SP), thereby providing an efficient psychophysical test of this phenomenon. ⋯ Temporal summation testing is rapidly becoming a relevant psychophysical tool for the study of chronic pain disorders. The results of this study will allow more efficient use of currently available constant-contact thermodes for clinical and research applications.
-
A cross-sectional design across late childhood and adolescence examined the influence of sex, gender socialization, and age on responses to controlled laboratory pain tasks. Healthy children and adolescents (n = 240, 50% female, age 8 to 18 years) completed the Child Sex Role Inventory, a self-report measure of identification with stereotypically masculine and feminine personality traits, as an index of gender socialization and participated in pressure, cold pressor, and heat pain tasks. Pain tolerance, pain intensity, and bothersomeness of each pain task were assessed. Masculinity correlated with lower heat pain ratings in boys but not girls. Logistic regression indicated cold pain intensity ratings were predicted by sex, gender score, and the age-by-gender score interaction. Heat pain intensity was predicted by age, gender score, age-by-gender score interaction, and sex-by-gender score. ⋯ The current findings support closer examination of the influence of gender socialization on young people's pain responses and highlight the importance of a multifactorial, developmental approach to studying the impact of gender socialization on the emergence of sex differences in pain responses after puberty.