Pain
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Randomized Controlled Trial
Enhanced affect/cognition-related brain responses during visceral placebo analgesia in irritable bowel syndrome patients.
Placebo analgesia is a psychosocial context effect that is rarely studied in visceral pain. Patients with irritable bowel syndrome (IBS) exhibit visceral hyperalgesia and heightened affective/cognitive brain region activation during visceral stimuli. Psychological factors alter the pain and brain activation pattern, and these changes are more pronounced in IBS patients. ⋯ VLPFC was also more active during anticipation in IBS patients. In conclusion, IBS patients and control subjects achieved comparable placebo analgesia during experimentally induced rectal pain. The visceral placebo analgesia produced heightened activity in affective/cognitive brain regions in IBS patients.
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Recently, a self-rating measure for pain perception based on imagined painful daily life situations, the Pain Sensitivity Questionnaire (PSQ), has been developed and shown to correlate with experimentally obtained pain intensity ratings in healthy subjects. Here, we assessed the validity of the PSQ for investigation of general pain perception (ie, pain perception outside the site of clinical pain) in chronic pain patients. PSQ scores were obtained in 134 chronic pain patients and compared to those of 185 healthy control subjects. ⋯ Results show that PSQ scores were significantly correlated with both experimental pain intensity ratings (Pearson's r=0.71, P<.001) and experimental pain thresholds (r=-0.52, P<.001). In addition, chronic pain patients exhibited significantly elevated PSQ scores as compared to healthy controls, consistent with the generalized increase of experimentally determined pain perception that has repeatedly been reported in chronic pain patients. These results demonstrate that the PSQ constitutes a valid self-rating measure of pain perception outside the clinical pain site in chronic pain patients and might serve as an alternative to experimental assessment of pain perception outside the clinical pain site in situations where experimental pain testing is not feasible.
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Clinical Trial
Opioid-independent mechanisms supporting offset analgesia and temporal sharpening of nociceptive information.
The mechanisms supporting temporal processing of pain remain poorly understood. To determine the involvement of opioid mechanisms in temporal processing of pain, responses to dynamic noxious thermal stimuli and offset analgesia were assessed after administration of naloxone, a μ-opioid antagonist, and on a separate day, during and after intravenous administration of remifentanil, a μ-opioid agonist, in 19 healthy human volunteers. Multiple end points were sampled from real-time computerized visual analog scale ratings (VAS, 1 to 10) to assess thermal sensitivity, magnitude and duration of offset analgesia, and painful after sensations. ⋯ Because thermal hyperalgesia was observed after both drugs, 8 of the original 19 subjects returned for an additional session without drug administration. Thermal hyperalgesia and increased magnitude of offset analgesia were observed across conditions of remifentanil, naloxone, and no drug within this subset analysis, indicating that repeated heat testing induced thermal hyperalgesia, which potentiated the magnitude of offset analgesia. Thus, it is concluded that the mechanisms subserving temporal processing of nociceptive information are largely opioid-independent, but that offset analgesia may be potentiated by heat-induced thermal hyperalgesia in a proportion of individuals.
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Chronic low back pain (LBP) is a complex, multifactorial disorder with unclear underlying mechanisms. In humans and rodents, decreased expression of secreted protein acidic rich in cysteine (SPARC) is associated with intervertebral disc (IVD) degeneration and signs of LBP. The current study investigates the hypothesis that IVD degeneration is a risk factor for chronic LBP. ⋯ Morphine (6 mg/kg, i.p.) reduced cutaneous sensitivity and alleviated axial discomfort in SPARC-null mice. Ageing SPARC-null mice mirror many aspects of the complex and challenging nature of LBP in humans and incorporate both anatomic and functional components of the disease. The current study supports the hypothesis that IVD degeneration is a risk factor for chronic LBP.
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Accumulated evidence suggests that the C-C motif chemokine ligand 5 (CCL5) modulates migration of inflammatory cells in several pathological conditions. This study tested the hypothesis that lack of CCL5 would modulate the recruitment of inflammatory cells to painful, inflamed sites and could attenuate pain in a murine chronic neuropathic pain model. Nociceptive sensitization, immune cell infiltration, multiple cytokine expression, and opioid peptide expression in damaged nerves were studied in wild-type (CCL5 +/+) and CCL5-deficient (CCL5 -/-) mice after partial sciatic nerve ligation (PSNL). ⋯ We demonstrated that lack of CCL5 modulated cell infiltration and the proinflammatory milieu within the injured nerve. Attenuated behavioral hypersensitivity in CCL5 -/- mice observed in the current study could be a result of decreased macrophage infiltration, mobilization, and functional ability at injured sites. Collectively, the present study results suggest that CCL5 receptor antagonists may ultimately provide a novel class of analgesics for therapeutic intervention in chronic neuropathic pain.