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There has been controversy as to whether the contribution of descending fibers from the rostral ventromedial medulla to opioid analgesia depends on the nature of the noxious stimulus eliciting pain. In the present study, inactivation of descending fibers by microinjection of muscimol (50 ng) in the rostral ventromedial medulla abolished morphine analgesia in the tail immersion and hot plate tests but decreased morphine analgesia by 60% in the formalin test. Analysis of the dose-response relation for morphine after inactivation of descending fibers revealed that, except for the tail immersion test, high doses of morphine could not overcome the block induced by muscimol. Also, morphine analgesia elicited supraspinally was not detectable when descending fibers were inactivated, suggesting that the analgesic effect of morphine in the brain requires a relay via the rostral ventromedial medulla. The analgesic effect of buprenorphine also depends on the integrity of descending fibers from the rostral ventromedial medulla. The results indicate that descending fibers from the rostral ventromedial medulla are critically important to the analgesic effect of opioids, regardless of the type of noxious stimulation eliciting pain. Residual analgesic effects of opioids after inactivation of descending fibers may be due to peripheral effects in the presence of inflammation.

Compared to rats that were given three daily sessions of habituation to a laboratory environment, non-habituated rats were behaviourally less reactive when pain was produced by 0.05 ml of 2.5% formalin injected s.c. in one hindpaw. This behavioural analgesia was equivalent to that produced by approximately 2.0 mg/kg morphine and was interpreted as analgesia induced by the stress of exposure to a novel environment. Methysergide (10 mg/kg) or 1-valine (200 mg/kg) alone, or combined with naloxone (0.1 or 2.0 mg/kg), reversed the effect of exposure to a novel environment. Naloxone itself had no significant effect. In habituated rats 1-valine reduced the response to formalin-induced pain whereas methysergide combined with naloxone increased it. It is concluded that analgesia induced by the stress of exposure to a novel environment depends on serotonin.

Guanethidine treatment decreased morphine analgesia exhibited by restrained rats but had no effect on morphine analgesia exhibited by unrestrained rats or on baseline pain sensitivity. Guanethidine also prevented the rise in tryptophan uptake into the brain induced by the restraint stress. It is argued that the prevention of the stress-induced increase in brain tryptophan uptake is causal to guanethidine's attenuation of morphine analgesia exhibited by restrained rats, since the increase in brain typtophan uptake has already been shown to be critical to this phenomenon. The blockade of the stress-induced increase in brain tryptophan uptake and morphine analgesia by guanethidine support the hypothesis that these effects depend upon sympathetic activity.