Pain
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Comparative Study
Relationship between sodium channel NaV1.3 expression and neuropathic pain behavior in rats.
A multitude of voltage-gated sodium channel subtypes (NaV1) are expressed in primary sensory neurons where they influence excitability via their role in the generation and propagation of action potentials. Peripheral nerve injury alters the expression of several NaV1subtypes, but among these only NaV1.3 is up-regulated in dorsal root ganglia (DRG) neurons. The increased expression of NaV1.3 implicates this subtype in the development and maintenance of neuropathic pain, but its contribution to neuropathic pain behavior has not been examined. ⋯ We then selectively axotomized a cutaneous nerve (sural) and a muscle nerve (gastrocnemius) in order to identify if NaV1.3 up-regulation is dependent on cutaneous and/or muscle afferent activation and found that the numbers of neurons expressing NaV1.3 was proportional to the magnitude of the injury, but independent of the nature of innervation. These results suggest that NaV1.3 increases in primary sensory neurons that are not directly damaged in response to injury. Thus, although NaV1.3 is up-regulated in a subpopulation of DRG neurons after injury, reduction in the expression of NaV1.3 subtype alone is not sufficient to influence the NaV1-dependent behavioral hypersensitivity associated with nerve injury.
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Comparative Study
Pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test.
The possible pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test was assessed. Local administration of 5-HT7 (SB-269970, 2.5-77.1 nmol/paw), but not 5-HT(1A) (WAY-100635, 1-60 nmol/paw), receptor antagonist significantly reduced formalin-induced flinching. Local 5-hydroxytryptamine (5-HT, 3-100 nmol/paw) or 5-carboxamidotryptamine (5-CT, 0.3-3 nmol/paw) (a 5-HT7/1A receptor agonist) augmented, in a dose-dependent manner, 0.5% formalin-induced nociceptive behavior. ⋯ In addition, the spinal antinociceptive effect of 5-CT was partially reversed by WAY-100635 (10 nmol/rat). The spinal antinociceptive effect of 5-HT was unaffected either by SB-269970 (77 nmol/rat) or WAY-100635 (10 nmol/rat). Data suggest that 5-HT7, but not 5-HT1A, receptors play a pronociceptive role in peripheral and spinal sites in the rat formalin test.
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We developed a mouse model of cancer pain to investigate its underlying mechanisms. SCC-7, squamous cell carcinoma (SCC) derived from C3H mice, was inoculated subcutaneously into either the plantar region or thigh in male C3H/Hej mice. Heat and mechanical sensitivity as well as spontaneous behavior were measured at the plantar surface of the ipsilateral hind paw after the inoculation. ⋯ Intraperitoneal administration of the competitive TRPV1 antagonist capsazepine inhibited hyperalgesia induced by tumor cell-inoculation in either plantar- or thigh-inoculated animals. This study indicated that inoculation of SCC resulted in spontaneous pain, heat hyperalgesia and mechanical allodynia. The altered expression of TRPV1 in the DRG may be involved in behavioral changes in this model.