Articles: hyperalgesia.
-
The contribution of the peripheral nervous system to opiate-induced hyperalgesia (OIH) is not well understood. In this study, we determined the changes in excitability of primary sensory neurons after sustained morphine administration for 7 days. Changes in the expression of glutamate receptors and glutamate transporters after morphine administration were ascertained in dorsal root ganglions. ⋯ Coadministration in vivo of the GluN2B selective antagonist Ro 25-6981 with morphine for 7 days prevented the appearance of OIH and increased morphine-induced analgesia. Administration of morphine for 7 days led to an increased expression of GluN2B and excitatory amino acid transporter 3/excitatory amino acid carrier 1, but not of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate, kainate, or group I metabotropic glutamate receptors, or of the vesicular glutamate transporter 2. These results suggest that peripheral glutamatergic neurotransmission contributes to OIH and that GluN2B subunit of NMDA receptors in the periphery may be a target for therapy.
-
Resveratrol, a component of red wine, has been reported to decrease prostaglandin E2 production by inhibiting the cyclooxygenase-2 cascade and to modulate various voltage-dependent ion channels, suggesting that resveratrol could attenuate inflammatory hyperalgesia. However, the effects of resveratrol on inflammation-induced hyperexcitability of nociceptive neurons in vivo remain to be determined. Thus, the aim of the present study was to determine whether daily systemic administration of resveratrol to rats attenuates the inflammation-induced hyperexcitability of spinal trigeminal nucleus caudalis wide-dynamic range neurons associated with hyperalgesia. ⋯ These results suggest that chronic administration of resveratrol attenuates inflammation-induced mechanical inflammatory hyperalgesia and that this effect is due primarily to the suppression of spinal trigeminal nucleus caudalis wide dynamic range neuron hyperexcitability via inhibition of both peripheral and central cyclooxygenase-2 cascade signaling pathways. These findings support the idea of resveratrol as a potential complementary and alternative medicine for the treatment of trigeminal inflammatory hyperalgesia without side effects.
-
Although calcitonin gene-related peptide is a recognized pain transducer, the expression of calcitonin gene-related peptide in primary afferents may be differentially affected following different types of nerve injury. Here, we examined whether different calcitonin gene-related peptide expression patterns in primary afferents contributes to distinct sensory disturbances in three animal models of sciatic nerve injury: chronic constriction injury, mild (100 g force) or strong (1000 g force) transient crush in rats. Assessments of withdrawal reflexes and spontaneous behavior indicated that chronic constriction injury and mild crush resulted in positive neuropathic symptoms (static/dynamic mechanical allodynia, heat hyperalgesia, cold allodynia, spontaneous pain). ⋯ Moreover, nerve injury caused a subcellular redistribution of calcitonin gene-related peptide from small- and medium-size dorsal root ganglia neurons to large-size dorsal root ganglia neurons, which paralleled the development of positive neuropathic symptoms. Intrathecal administration of the calcitonin gene-related peptide receptor antagonist ameliorated these positive symptoms, indicating that the expression of calcitonin gene-related peptide in large-size dorsal root ganglia neurons is important for the positive neuropathic symptoms in all three models. Taken together, these results suggest that distinct calcitonin gene-related peptide expression pattern in primary afferents contribute to different neuropathic symptoms following chronic constriction or crush injuries to the rat sciatic nerve.
-
Peripheral neuropathy is a common adverse effect of paclitaxel and oxaliplatin treatment. The major dose-limiting side effect of these drugs is peripheral sensory neuropathy. The symptoms of paclitaxel-induced neuropathy are mostly sensory and peripheral in nature, consisting of mechanical allodynia/hyperalgesia, tingling, and numbness. ⋯ This review describes that (1) paclitaxel-induced neuropathic pain may be the result of up-regulation of TRPV1 in small- and medium-diameter DRG neurons. In addition, paclitaxel treatment increases the release of substance P, but not calcitonin gene-related peptide, in the superficial layers of the spinal dorsal horn. (2) TRPA1 expression via activation of p38 mitogen-activated protein kinase in small-diameter DRG neurons, at least in part, contributes to the development of oxaliplatin-induced acute cold hyperalgesia. We suggest that TRPV1 or TRPA1 antagonists may be potential therapeutic lead compounds for treating anticancer drug-induced peripheral neuropathy.
-
Topical high-dose capsaicin acting on TRPV1 receptors and inducing an intraepidermal decrease in the small nerve fibre count is effective in treating neuropathic pain (NP). Sensory changes after capsaicin application, their correlation with pain relief and their role as possible predictors of response have been insufficiently analysed. We hypothesized a positive correlation between pain relief and increase in the warmth detection threshold (WDT), indicating loss of C-fibre function, and higher response rates in patients with preserved C-fibre function or heat hyperalgesia before application. ⋯ Efficacy of capsaicin does not correlate with the induced loss of function of small fibres, measured by QST. Presence of cold and pinprick hyperalgesia seems to be predictive of response to capsaicin (8%).