Pain
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Randomized Controlled Trial
Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients.
The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. ⋯ However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.
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Randomized Controlled Trial
Experimental characterization of the effects of acute stresslike doses of hydrocortisone in human neurogenic hyperalgesia models.
Relative hypothalamic-pituitary-adrenal axis dysfunction has been described as a common feature of several dysfunctional pain syndromes, and its end hormone cortisol may thus constitute a protective factor against the development of chronic pain. We investigated the potential influence of experimentally induced stress-like hypercortisolism on the induction of neurogenic hyperalgesia using 2 human surrogate models: secondary hyperalgesia after intradermal capsaicin injection into the volar forearm, and perceptual windup in normal skin. In a double-blind, placebo-controlled, randomized, crossover study, a psychophysical study was performed in 10 healthy subjects (median age 23 years) examining the effects of 40 mg orally administered hydrocortisone. ⋯ Temporal summation (windup) to mechanical pain stimuli and electrically induced windup of second pain (tested in an independent cohort of 10 other subjects) were also unchanged. The selective effects of hydrocortisone on pinprick hyperalgesia but not pinprick pain suggest an antihyperalgesic rather than analgesic effect. The findings suggest that hypothalamic-pituitary-adrenal axis reactivity might be an important mechanism in resilience to dysfunctional pain syndromes.
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Multicenter Study
Patient perspective on herpes zoster and its complications: an observational prospective study in patients aged over 50 years in general practice.
Understanding the effect of herpes zoster and zoster-related pain should inform care to improve health-related quality of life in elderly patients. A 12-month, longitudinal, prospective, multicenter observational study conducted in primary care in France enrolled patients aged ≥ 50 years with acute eruptive herpes zoster. Patient-reported zoster-related pain was assessed by validated questionnaires (Douleur Neuropathique en 4 Questions [DN4], Zoster Brief Pain Inventory [ZBPI], and Neuropathic Pain Symptom Inventory [NPSI]) on days 0 and 15, and at months 1, 3, 6, 9, and 12. ⋯ Patients with persistent pain had lower scores on the physical and mental component summaries of the SF-12 and the ZBPI interference score than those without pain. By logistic regression analysis, main predictive factors on day 0 for postherpetic neuralgia at month 3 were age, male sex, ZBPI interference score, Physical Component Summary score of the SF-12, and neuropathic quality of pain (DN4 score ≥ 4). Despite early diagnosis and treatment with antiviral agents, many patients with herpes zoster experience persistent pain and marked long-term reduction in health-related quality of life.
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Menthol is a natural compound of plant origin known to produce cool sensation via the activation of the TRPM8 channel. It is also frequently part of topical analgesic drugs available in a pharmacy, although its mechanism of action is still unknown. Compelling evidence indicates that voltage-gated Na(+) channels are critical for experiencing pain sensation. ⋯ In current clamp recordings, menthol inhibited firing at high-frequency stimulation with minimal effects on normal neuronal activity. We found that low concentrations of menthol cause analgesia in mice, relieving pain produced by a Na(+) channel-targeting toxin. We conclude that menthol is a state-selective blocker of Nav1.8, Nav1.9, and TTX-sensitive Na(+) channels, indicating a role for Na(+) channel blockade in the efficacy of menthol as topical analgesic compound.
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Effector CD4(+) T lymphocytes generated in response to antigens produce endogenous opioids. Thus, in addition to their critical role in host defenses against pathogens, effector CD4(+) T lymphocytes contribute to relieving inflammatory pain. In this study, we investigated mechanisms of opioid release by antigen-experienced effector CD4(+) T cells that leave draining lymph nodes and come back into the inflammatory site. ⋯ Analgesia was observed by transferring effector CD4(+) T lymphocytes with Th1 or Th2 phenotype, suggesting that antinociceptive activity is a fundamental property of effector CD4(+) T lymphocytes irrespective of their effector functions. Based on the use of agonists and antagonists selective for each of the opioid receptor subclasses, we showed that analgesia induced by T cell-derived opioids is elicited via activation of δ-type opioid receptors in the periphery. Thus, the antinociceptive activity is a fundamental property associated with the effector phase of adaptive immunity, which is driven by recognition of the cognate antigen by effector CD4(+) T lymphocytes at the inflammatory site.