Pain
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N-type calcium channels modulate the release of key pro-nociceptive neurotransmitters such as glutamate and substance P (SP) in the central nervous system. Considerable research interest has focused on the therapeutic potential of the peptidic omega-conopeptides, GVIA and MVIIA as novel analgesic agents, due to their potent inhibition of N-type calcium channels. Recently, the novel peptidic N-type calcium channel blocker, AM336, was isolated from the venom of the cone snail, Conus catus. ⋯ Following acute i.t. dosing, AM336 evoked dose-dependent antinociception (ED50 approximately 0.110 nmol) but the doses required to produce side-effects were an order of magnitude larger than the doses required to produce antinociception. For i.t. doses of MVIIA
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The aim of this study was to develop a rat model of capsaicin-induced pain in the orofacial region. We examined the effects of subcutaneous injection of different doses of capsaicin (0.25, 0.4, 0.8, 1.5, 2.5, 25, 50, 100, 500 microg) on the face-grooming response. Injection of capsaicin into the vibrissa pad produced an immediate grooming of the injected area with ipsilateral fore- or hindpaw. ⋯ The local administration of morphine (ED(50): 0.65 mg/kg) was more potent than systemic injection (ED50: 2.54 mg/kg) in reducing the grooming behavior. In conclusion, the orofacial capsaicin test appears to be a valid and reliable method for studying trigeminal pain mechanisms and testing analgesic drugs. The results of the present study also support the clinical use of peripheral opioid administration for the treatment of orofacial painful conditions.
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The goal of the present study was to identify nuclei of the amygdala in which opioid-sensitive systems can act to recruit nociceptive modulatory circuitry in the rostral ventromedial medulla (RVM) and affect nociceptive responsiveness. In lightly anesthetized rats, 10 microg of morphine was bilaterally microinjected into basolateral, cortical, medial, central, and lateral nuclei of the amygdala to determine the relative influence on the activity of identified ON, OFF and NEUTRAL cells in the RVM and on the latency of the tail flick reflex evoked by noxious radiant heat. Infusions of morphine into the basolateral nuclei resulted in a substantial, naloxone-reversible increase in tail flick latency, and significantly increased ongoing firing of OFF cells and depressed that of ON cells. ⋯ Opioid action within the medial and cortical nuclei also influenced RVM cell activity, but did not prevent the reflex-related OFF cell pause, and failed to alter the tail flick substantially. These observations, plus the lack of an opioid-activated influence from the central and lateral nuclei, demonstrate fundamental differences among systems linking the different amygdalar nuclei with the RVM. One way in which the modulatory circuitry of the RVM might be engaged physiologically in behaving animals is via opioid-mediated activation of the basolateral nucleus.
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This study describes the first known model of bone cancer pain in the rat. Sprague-Dawley rats receiving intra-tibial injections of syngeneic MRMT-1 rat mammary gland carcinoma cells developed behavioural signs indicative of pain, including: mechanical allodynia, difference of weight bearing between hind paws and mechanical hyperalgesia. The development of the bone tumour and structural damage to the bone was monitored by radiological analysis, quantitative measurement of mineral content and histology. ⋯ In summary, the induction of bone cancer in the rat by the syngeneic MRMT-1 mammary tumour cell line provides a valid pre-clinical model for pain associated with bone metastases. Significant mechanical hyperalgesia and allodynia develops in association with the progression of the tumour in the bone marrow cavity, while the general condition of the animal remains satisfactory. While acute treatment with morphine has some analgesic effect on hind limb sparing the selective COX-2 inhibitor, celebrex, has no influence on the pain-related behavioural changes in this model.