Pain
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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.
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Comparative Study Clinical Trial
Long-term cohort study comparing medical (oxcarbazepine) and surgical management of intractable trigeminal neuralgia.
Trigeminal neuralgia is a recurrent severe shooting neuropathic pain which can be managed both pharmacologically and surgically. However, there are no prospective data that compare these two therapeutic strategies. This study therefore aimed to assess long-term outcome in patients with intractable trigeminal neuralgia treated with oxcarbazepine and later with surgery. ⋯ Surgery does not provide pain relief for all patients. This is the first study that has compared outcome in a group of patients who have had both pharmacological and surgical treatments. As these data cannot be extrapolated to other antineuralgic drugs, similar comparative studies would be appropriate.
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To study the role of inflammatory cytokines in the initiation and persistence of radiculopathy as seen in humans, tumor necrosis factor alpha (TNF-alpha) was administered either to normal, uninjured L5 dorsal root ganglia (DRG) of rats via a hole drilled through the transverse process, or to chronically compressed L5 DRG via a hollow stainless steel rod inserted into the intervertebral foramen. In other experiments, a mixture of soluble TNF receptors (sTNF-Rs: sTNF-RIplus minussTNF-RII) was locally delivered to the chronically or acutely compressed DRG to neutralize the activity of endogenous TNF-alpha. Behavioral tests of mechanical allodynia were performed before and after TNF-alpha administration. ⋯ Similar results were obtained when sTNF-Rs were chronically administrated at the acutely compressed ganglion. Results demonstrated that exogenous TNF-alpha causes pain and mechanical allodynia when deposited at the normal DRG, and further enhances the ongoing allodynia when administrated at the compressed DRG. Results also suggest that endogenous TNF-alpha contributes to the early development of mechanical allodynia in rats with chronic DRG compression.