Articles: hyperalgesia.
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Widespread deep tissue pain hyperalgesia was evaluated in women with chronic whiplash associated disorder (n = 25) and controls (n = 10) using computerized cuff pressure algometry and hypertonic saline infusion. ⋯ The results indicated widespread hyperalgesia in chronic whiplash associated disorder and facilitated temporal summation outside the primary pain area, suggesting involvement of central sensitization.
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The NMDA and TRPV1 receptors that are expressed in sensory neurons have been independently demonstrated to play important roles in peripheral pain mechanisms. In the present study, we investigated whether the 2 receptor-channel systems form a functional complex that provides the basis for the development of mechanical hyperalgesia. In the masseter muscle, direct application of NMDA induced a time-dependent increase in mechanical sensitivity, which was significantly blocked when the muscle was pretreated with a specific TRPV1 antagonist, AMG9810. ⋯ Consistent with the biochemical data, the NMDA-induced mechanical hyperalgesia was also effectively blocked when the muscle was pretreated with a CaMKII or PKC inhibitor. Thus, NMDA receptors and TRPV1 functionally interact via CaMKII and PKC signaling cascades and contribute to mechanical hyperalgesia. These data offer novel mechanisms by which 2 ligand-gated channels in sensory neurons interact and reinforce the notion that TRPV1 functions as a signal integrator under pathological conditions.
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Brain research bulletin · Jul 2012
High-mobility group box 1 contributes to mechanical allodynia and spinal astrocytic activation in a mouse model of type 2 diabetes.
Chronic pain is one of the most common complications of diabetes. However, current treatments for diabetic pain are usually unrealistic because the underlying mechanisms are far from being clear. Immerging studies have implicated immune factors as key players in the diabetic pain. ⋯ Anti-HMGB1 could effectively decrease GFAP expression. Real-time PCR showed that in postnatal 4 months, db/db mice induced significant increases of TNF-alpha, IL-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) in the spinal dorsal horn, while anti-HMGB1 (50 μg) effectively inhibited the up-regulation of these inflammatory mediators. Our results indicate that HMGB1 is significantly up-regulated in the spinal cord of type 2 diabetes, and inhibiting HMGB1 may provide a novel treatment for diabetic pain.
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N-palmitoyl-ethanolamine (PEA) is an endogenous substance that was first identified in lipid tissue extracts. It has been classified as a CB(2) receptor agonist. Exogenous PEA has the potential to become a valid treatment for neuropathic and inflammatory pain. ⋯ In addition, the dosage of nitrite in the homogenized paw, as determined by colorimetric assay, indicated that exogenous PEA is able to induce NO release. The soluble guanylyl cyclase inhibitor ODQ antagonized the PEA effect, whereas the cGMP-phosphodiesterase inhibitor zaprinast potentiated the antinociceptive effect of low-dose PEA. This study provides evidence that PEA activates nNOS, thus initiating the NO/cGMP pathway and inducing peripheral antinociceptive effects.
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The current study was designed to evaluate therapeutic potential of systemically administered ethanolic and aqueous extracts of saffron as well as its bioactive ingredients, safranal and crocin, in chronic constriction injury (CCI)-induced neuropathic pain in rats. The von Frey filaments, acetone drop, and radiant heat test were performed to assess the degree of mechanical allodynia, thermal allodynia and thermal hyperalgesia respectively, at different time intervals, i.e., one day before surgery and 3, 5, 7 and 10 days post surgery. The ambulatory behavior was evaluated using the open field test. ⋯ Crocin even at the high dose (50 mg/kg) failed to produce any protective role. However, gabapentine (100 mg/kg) as a reference drug significantly alleviated all behavioral manifestations of neuropathic pain compared to control group. In conclusion, the results of this study suggest that ethanolic and aqueous extracts of saffron as well as safranal could be useful in treatment of different kinds of neuropathic pains and as an adjuvant to conventional medicines.