Brain research
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Analgesia can be elicited following microinjections of morphine, mu-selective agonists and beta-endorphin into the amygdala. These analgesic responses are mediated by opioid synapses in the periaqueductal gray (PAG) since general (naltrexone), mu (beta-funaltrexamine) and delta2 (naltrindole isothiocyanate) opioid antagonists administered into the PAG significantly reduce both morphine and beta-endorphin analgesia elicited from the amygdala. Supraspinal multiplicative opiate analgesic interactions have been observed between the PAG and rostroventromedial medulla (RVM), the PAG and locus coeruleus (LC), and the RVM and LC. ⋯ Co-administration of beta-endorphin (1 microg) into the amygdala and morphine (1 microg) into the PAG produced a potent interaction, but co-administration of morphine (1 microg) into the amygdala and beta-endorphin (1 microg) into the PAG failed to produce interactive effects. Finally, co-administration of morphine (1 microg) and beta-endorphin (1 microg) into either the amygdala alone or the PAG alone failed to produce an interaction, indicating the importance of regional opioid activation. These data are discussed in terms of the test-specificity of nociceptive processing in the amygdala, in terms of the multiple modulatory mechanisms mediating beta-endorphin analgesia in the PAG, and in terms of whether the interactions are either mediated by anatomical connections between the amygdala and PAG or by mechanisms initiated by these two sites converging at another site or sites.
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The amygdala, periaqueductal gray (PAG), and rostral ventromedial medulla (RVM) are critical for the expression of some forms of stress-related changes in pain sensitivity. In barbiturate anesthetized rats, microinjection of agonists for the mu opioid receptor into the amygdala results in inhibition of the tail flick (TF) reflex evoked by radiant heat. We tested the idea that TF inhibition following opioid stimulation of the amygdala is expressed through a serial circuit which includes the PAG and RVM. ⋯ Since acute injection of lidocaine into the RVM also affected baseline heart rate, separate animals were prepared with small electrolytic lesions placed in the RVM. Chronic RVM lesions also blocked TF inhibition produced by amygdala stimulation but did not affect heart rate. These results, when taken together with similar findings in awake behaving animals, suggest that a neural circuit which includes the amygdala, PAG, and RVM is responsible for the expression of several forms of hypoalgesia in the rat.
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Peripheral tissue injury results in a change in the excitability of spinal dorsal horn neurons, central sensitization, and the behavioral correlate, hyperalgesia. It is proposed here that a dynamic balance exists between excitatory and inhibitory synaptic input to the spinal dorsal horn that functions to prevent central sensitization following brief, mild, noxious stimulation. Following more severe stimulation and injury, there is a loss of these inhibitory mechanisms that allow central sensitization to proceed. ⋯ It is suggested that this attenuation, whether or not expressed, prevents a significant portion of deep dorsal horn neurons from becoming sensitized to C-fiber input. This functions to prevent central sensitization when the noxious stimulus does not produce inflammation and it is not beneficial to the animal to become hyperalgesic (i.e., to alter its behavior in order to protect an injured limb and reduce painful sensations). Following injury-producing tissue damage and inflammation the mechanisms that produce the attenuation are reduced, with a concomitant increase in excitation to electrical and natural stimuli, suggesting that the attenuation is inhibitory modulation of nociceptive input and injury results in a disinhibition producing an increase in excitability and central sensitization.
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We developed an assay which predicts the antimigraine efficacy of sumatriptan. Our assay is based on two assumptions: (1) electrical stimulation of the trigeminal ganglion mimics the neurogenic inflammatory process and (2) stimulation-induced increases in n. trigeminal caudalis blood flow reflect activation of a large population of neurons. ⋯ Sumatriptan blunted the increase in blood flow following stimulation of the trigeminal ganglion. These data suggest that the n. trigeminal caudalis blood flow model may be useful in identifying antimigraine compounds.
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This study examined estrous differences in the characteristics of behavioral crises of visceral pain in female rats video-taped throughout a 4-day period after implantation of an artificial stone in one ureter. All animals continued to have a regular cycle after ureteral surgery. ⋯ Mean duration and complexity of crises were slightly higher in M/D than in P/E, but the difference was not significant. The results in this animal model show an enhancement of ureteral pain sensitivity in M/D, a finding in line with the clinical observation, in fertile women with urinary calculosis, of a greater incidence of colics in the perimenstrual period (equivalent to M/D in rats).