Cats produce analgesia in rats on the tail-flick test: naltrexone sensitivity is determined by the nociceptive test stimulus

Previous research has demonstrated that exposure to a cat produces a naltrexone-reversible antinociception as assessed in the formalin test in rats. Because different neurochemical mechanisms inhibit different forms of nociception, the present study examined whether presentation of a cat would also produce a naltrexone-reversible antinociception in the tail-flick response to radiant heat and electric shock. Exposure to the cat produced antinociception in both tail-flick paradigms. Naltrexone blocked the inhibition of the thermally evoked tail-flick response, but had no effect in the electric shock tail-flick paradigm. These results indicate that opioid mediation of stress-induced analgesia is determined, in part, by the nociceptive test employed.     

Evidence for opioid and non-opioid forms of stress-induced analgesia in the snail, Cepaea nemoralis

Exposure to either cold or warm stress increased the thermal nociceptive thresholds of the terrestrial snail, Cepaea nemoralis. The warm stress-induced 'analgesia' was blocked by the prototypic opiate antagonist, naloxone, and the delta-opiate antagonist, ICI 154,129, and was suppressed by a 24-h pretreatment with the irreversible opiate antagonist, beta-funaltrexamine (B-FNA). In contrast, cold stress-induced analgesia was unaffected by either naloxone, ICI 154,129 or B-FNA. These results indicate that this mollusc displays both opioid and non-opioid forms of stress-induced analgesia in a manner analogous to that reported for mammals. These findings suggest an early evolutionary development and phylogenetic continuity of opioid and non-opioid mediated stress responses to aversive environmental stimuli.     

Spinal and supraspinal opioid analgesia in the mouse: the role of subpopulations of opioid binding sites

The selective in vivo blockade of high affinity (mu1) opioid binding sites in mice by naloxazone reduced the analgesic potency of opiates and opioid peptides, evidenced by a shift of their analgesic ED50 values. However, the extent of these shifts varied significantly between a series of opioid drugs, ranging from 12-fold for morphine to 4-fold for D-Ala2-D-Leu5-enkephalin. These findings suggested that analgesia in naloxazone-treated animals is mediated through a different subpopulation of receptors than in normal controls. Correlating these analgesic shifts for a series of opioids with their affinity for different [3H]opioid binding sites suggested an analgesic role for delta sites. Additional studies in mice with spinal transections suggested that mu1 analgesia was primarily supraspinal.     

Stress-induced release of brain and pituitary β-endorphin: Major role of endorphins in generation of hyperthermia, not analgesia

The present paper examines the conjectured causal relationship between the alterations in brain, pituitary and plasma levels of endorphins and the antinociception (analgesia) and hyptermia elicited by acute stress. A 5-min foot-shock instigated a significant depression in the levels of β-endorphin immunoreactivity (β-EI) in both the hypothalamus and periventricular β-endorphinergic fibre-containing tissue. A large elevation in plasma levels of β-EI, consisting of about 70% β-endorphin (β-EP), and 30% β-lipotropin (β-LPH) was associated with a significant reduction in the β-EI content of both the anterior (AL) and neurointermediate (NIL) lobes of the pituitary. No concomitant changes in the levels of Met-enkephalin immunoreactivity (M-EI) in discrete areas of brain and pituitary were detectable. Application of high (10 mg/kg) but not a low (1 mg/kg) dose of naloxone, prior to foot-shock, slightly reduced the increase in tail-flick latency evoked by this stress. In contrast, both of these doses strongly and dose-dependently attenuated the accompanying rise in core temperature (Tc). Chronic (30 day) morphine treatment resulted in a 45% decrease in the NIL content of β-EI and a clear depression in its basal plasma levels, although a substantial post-stress rise in plasma β-EI was still found: stress-induced analgesia (SIA) was enhanced, but the concurrent stress-induced hyperthermia (SIH), reduced in morphinized animals. These data demonstrate that stress produces a generalized mobilization of both central and pituitary pools of β-EI, and indicate that endorphins may play a more important role in the mediation of changes in Tc than in the generation of the concomitant increase in nociceptive threshold, upon activation by stress.     

The antinociceptive action of an α2-adrenoceptor agonist in the spinal dorsal horn is due to a direct spinal action and not to activation of Descending Inhibition

In this electrophysiological study we tried to find out whether the spinal antinociceptive effect of a supraspinaly administered α₂-adrenoceptor agonist is due to a direct spinal effect or to activation of descending inhibition. The responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were studied following application of medetomidine, a selective α₂-adrenergic agonist, into the rostroventromedial medulla (RVM) or directly onto the spinal cord of the Intact and in spinal rats. The noxious electrical stimuli were applied to the ipsilateral receptive field in the plantar region of the hind paw, and responses mediated by A- and C-fibers to WDR neurons were separately evaluated. The reversal of medetomidine-induced effects was attempted by a systemic administration of atipamezole, a selective α₂-adronoceptor antagonist. Medetomldine injection into the RVM produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses to WDR neurons of the spinal dorsal horn in both intact and spinal rats. Paradoxically, the spinal aMFnociceptive effect of supraspinally administered medstomidine was stronger in spinal rats. The A-fiber-mediated responses were significantly less attenuated by medetomidine than the C-fiber-mediated responses to the WDR neurons. Also a direct application of medetomidine onto the spinal cord produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses, and this effect was identical in intact and in spinal rats. The medetomidins doses producing spinal antinociception were considerably lower with a direct spinal application than with a supraspinal application. These results indicate that spinal antinocicsption following spinal or supraspinal application of an α₂-adrenergic agonist is due to a direct activation of spinal α₂-adrenoceptors and not to descending inhibition. Activation of supraspinal α₂-adrenoceptors counteracts the spinal antinociceptive effect.