Articles: hyperalgesia.
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The impaired attenuation of pain by the application of a noxious conditioning stimulus at a segmentally distinct site, known as conditioned pain modulation (CPM), has been implicated in clinical pain states. Chronic lateral epicondylalgia (LE), which is characterized by lower pressure pain thresholds (PPTs) at sites remote to the affected elbow and spinal cord hyperexcitability, is a clinical pain state that might plausibly involve less efficacious CPM. This study aimed to determine whether LE exhibits a less efficacious CPM compared with that in pain-free controls. ⋯ The results that suggest an impaired ability to modulate pain might be associated with the previously observed spinal cord hyperexcitability and the mechanical hyperalgesia that characterizes LE.
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Journal of anesthesia · Oct 2017
The preventive effects of dexmedetomidine on endotoxin-induced exacerbated post-incisional pain in rats.
Low-grade endotoxin (lipopolysaccharide; LPS) exposure may contribute to the development of exaggerated acute postoperative pain. In the present study, we investigated the possible impact of intraoperative administration of dexmedetomidine (DEX) on LPS-induced postoperative hyperalgesia in a rat incisional pain model. ⋯ Our findings indicate that intraoperative DEX treatment can prevent LPS-induced exacerbated post-incisional pain via the α2-adrenergic receptor signaling pathway.
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Painful peripheral neuropathy is a common side effect of paclitaxel (PTX). The use of analgesics is an important component for management of PTX-induced peripheral neuropathy (PINP). However, currently employed analgesics have several side effects and are poorly effective. β-caryophyllene (BCP), a dietary selective CB2 agonist, has shown analgesic effect in neuropathic pain models, but its role in chemotherapy-induced neuropathic pain has not yet been investigated. ⋯ Spinal cord immunohistochemistry revealed that preventive treatment with BCP reduced p38 MAPK and NF-κB activation, as well as the increased Iba-1 and IL-1β immunoreactivity promoted by PTX. Our findings show that BCP effectively attenuated PINP, possibly through CB2-activation in the CNS and posterior inhibition of p38 MAPK/NF-κB activation and cytokine release. Taken together, our results suggest that BCP could be used to attenuate the establishment and/or treat PINP.
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Brain research bulletin · Oct 2017
Downregulations of TRPM8 expression and membrane trafficking in dorsal root ganglion mediate the attenuation of cold hyperalgesia in CCI rats induced by GFRα3 knockdown.
Cold hyperalgesia is an intractable sensory abnormality commonly seen in peripheral neuropathies. Although glial cell line-derived neurotrophic factor family receptor alpha3 (GFRα3) is required for the formation of pathological cold pain has been revealed, potential transduction mechanism is poorly elucidated. We have previously demonstrated the contribution of enhanced activity of transient receptor potential melastatin 8 (TRPM8) to cold hyperalgesia in neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve. Recently, the enhancement of TRPM8 activity is attributed to the increased TRPM8 plasma membrane trafficking. In addition, TRPM8 can be sensitized by the activation of GFRα3, leading to increased cold responses in vivo. The aim of this study was to investigate whether GFRα3 could influence cold hyperalgesia of CCI rats via modulating TRPM8 expression and plasma membrane trafficking in dorsal root ganglion (DRG). ⋯ Our results demonstrate that GFRα3 knockdown specially inhibits cold hyperalgesia following CCI via decreasing the expression level and plasma membrane trafficking of TRPM8 in DRG. GFRα3 and its downstream mediator, TRPM8, represent a new analgesia axis which can be further exploited in sensitized cold reflex under the condition of chronic pain.
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The role of nitric oxide (NO) in nociceptive transmission at the spinal cord level remains uncertain. Increased activity of spinal N-methyl-d-aspartate (NMDA) receptors contributes to development of chronic pain induced by peripheral nerve injury. In this study, we determined how endogenous NO affects NMDA receptor activity of spinal cord dorsal horn neurons in control and spinal nerve-ligated rats. ⋯ Additionally, intrathecal injection of l-arginine significantly attenuated mechanical or thermal hyperalgesia induced by nerve injury, and the l-arginine effect was diminished in rats treated with a nNOS inhibitor or nNOS-specific siRNA. These findings suggest that endogenous NO inhibits spinal NMDA receptor activity through S-nitrosylation. NO derived from nNOS attenuates spinal nociceptive transmission and neuropathic pain induced by nerve injury.