Pain
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Oxidized linoleic acid metabolites (OLAMs) are a class of endogenous transient receptor potential vanilloid 1 (TRPV1) channel agonists released on exposure of tissue to transient noxious temperatures. These lipid compounds also contribute to inflammatory and heat allodynia. Because persistent pain after a burn injury represents a significant clinical challenge for treatment, we developed an in vivo rat model of partial-thickness cutaneous thermal injury and examined whether TRPV1 and specific OLAM metabolites play a role in mediating postburn pain injury. ⋯ Additional studies of the metabolism of [C(14)]-linoleic acid in skin biopsies revealed the role of the cytochrome P450 (CYP) system in mediating the metabolism of linoleic acid after thermal injury. Finally, we demonstrated that direct inhibition of OLAMs using OLAM antibodies and indirect inhibition using the CYP inhibitor ketoconazole significantly reduced postburn thermal allodynia. Collectively, these findings point to a novel role of the OLAMs and CYP-related enzymes in generating postburn allodynia via activation of peripheral TRPV1.
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The objectives of the current study were to describe fibromyalgia patient-spouse incongruence regarding patient pain, fatigue, and physical function; and to examine the associations of individual and interpersonal factors with patient-spouse incongruence. Two hundred four fibromyalgia patients and their coresiding partners rated the patient's symptoms and function. Multilevel modeling revealed that spouses, on average, rated patient fatigue significantly lower than patients. ⋯ An important within-couple interaction was found for pain interference, suggesting that couples who are similar on level of communication problems experience low incongruence; those with disparate ratings of communication problems experience high incongruence. Findings suggest the important roles of spouse response and the patient's perception of how well the couple is communicating. Couple-level interventions targeting communication or other interpersonal factors may help to decrease incongruence and lead to better patient outcomes.
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The aim of this study was to assess the function of the thermo-nociceptive system in 25 patients with long-lasting, medium-to-severe refractory complex regional pain syndrome (CRPS)-1 using behavioral (detection rates and reaction times) and electrophysiological (event-related brain potentials) responses to brief (50 milliseconds) and intense (suprathreshold for Aδ-nociceptors) carbon dioxide laser stimuli delivered to the affected and contralateral limbs, and by comparing these responses to the responses obtained in the left and right limbs of age- and sex-matched healthy controls. Compared with healthy controls and compared with the contralateral limb, the detection rate of pricking pain related to the activation of Aδ-fibers was markedly reduced at the affected limb. Furthermore, reaction times were substantially prolonged (>100 milliseconds in 84% of patients and >300milliseconds in 50% of patients). ⋯ Taken together, our results show that in the majority of patients with chronic CRPS-1, thermo-nociceptive pathways are dysfunctional. A number of pathological mechanisms involving the peripheral nervous system and/or the central nervous system could explain our results. However, the primary or secondary nature of these observed changes remains an open question.
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Randomized Controlled Trial
Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia.
Because transcutaneous electrical nerve stimulation (TENS) works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo-controlled cross-over design to test the effects of a single treatment of TENS with people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS and no TENS. ⋯ No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to the way in which TENS is used clinically on pain, fatigue, function, and quality of life in individuals with fibromyalgia.
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Peripheral neural mechanisms underlying the sensations of irritation, discomfort, and itch accompanying the eye allergic response have not been hitherto analyzed. We explored this question recording the changes in the electrical activity of corneoconjunctival sensory nerve fibers of the guinea pig after an ocular allergic challenge. Sensitization was produced by i.p. ovalbumin followed by repeated application in the eye of 10% ovalbumin on days 14 to 18. ⋯ Only capsazepine attenuated tearing rate increase and sensitization of the polymodal nociceptors response to CO2. Capsazepine also prevented the decrease in cold thermoreceptor activity caused by the allergic challenge. We conclude that changes in nerve impulse activity accompanying the ocular allergic response, primarily mediated by activation of nociceptor's TRPV1 and to a lesser degree by activation of TRPA1 channels, explain the eye discomfort sensations accompanying allergic episodes.