Intrinsic Mechanisms of Pain Inhibition: Activation by Stress

Abstract

Portions of the brain stem seem normally to inhibit pain. In man and laboratory animals these brain areas and pathways from them to spinal sensory circuits can be activated by focal stimulation. Endogenous opioids appear to be implicated although separate nonopioid mechanisms are also evident. Stress seems to be a natural stimulus triggering pain suppression. Properties of electric footshock have been shown to determine the opioid or nonopioid basis of stress-induced analgesia. Two different opioid systems can be activated by different footshock paradigms. This dissection of stress analgesia has begun to integrate divergent findings concerning pain inhibition and also to account for some of the variance that has obscured the reliable measurement of the effects of stress on tumor growth and immune function.

Burrowing as a non‐reflex behavioural readout for analgesic action in a rat model of sub‐chronic knee joint inflammation

“…While the significant improvement in WB at the equivalent high-dose pregabalin indicated that it provided a successful analgesic effect, the potential sedative side effects observed at this dose in the OF and burrowing assays suggest that this result was confounded and may represent a false positive resulting from the sedative effects of the drug. In contrast to the WB assay, the burrowing assay may not result in potential false positives/negatives induced by restraining the animal (Terman et al, 1984;Imbe et al, 2006;Mogil, 2009). The burrowing assay could, therefore, be used to discriminate between analgesic doses that impair movement, which according to previous reports, the WB assay cannot (Andrews et al, 2012).…”

“…As the animal is restrained, data from the WB assay do not distinguish between doses of sedatives that might impair movement and motor function. It has also been suggested that assays that restrain animals could elicit a stress response (Mogil, 2009), leading to increased pain tolerance due to stress-induced analgesia (Terman et al, 1984) or increased sensitivity to pain due to stress-induced hyperalgesia (Imbe et al, 2006). Stress-induced analgesia/hyperalgesia could, therefore, lead to false positives/negatives.…”

“…Rodents were presented with a gravel-filled hollow tube; the weight of gravel displaced from the tube after a fixed time period was measured and this weight was relative to the burrowing response (Deacon, 2006(Deacon, , 2009. The burrowing assay is considered to have advantages compared with evoked response or weight-bearing (WB) assays, which can potentially produce false positives/ negatives due to potential stress-induced responses, investigator bias and sedative side effects (Terman et al, 1984;Imbe et al, 2006;Mogil, 2009). To date, no comparison of the burrowing assay with established methods has been performed.…”

Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

“…They, and others, have reported that descending inhibitory systems are suppressed by barbiturates (Frank and Ohta 1971;Collins et al 1990). Since these reports, others showed that pentobarbital blocks shock-induced analgesia (Terman et al 1984;Grau 1987) and other forms of anesthesia were shown to diminish the inhibition of dorsal horn neuron firing seen after noxious stimulation (Tomlinson et al 1983). The exact mechanism through which this occurs remains unknown, although the inhibitory neurotransmitter GABA appears to play a major role (Asana and Ogasawara 1981;Olsen and Snowman 1982;Sivam et al 1982).…”

“…The inhibitory signal, is believed to originate in the periaqueductal gray, travel to the rostroventral medulla, including the nucleus raphe magnus (NRM), and then to the spinal cord through serotonergic fibers that descend through the DLF to suppress firing of neurons within the dorsal horns (Mayer et al 1971;Oliveras et al 1974;Fields 1979, 1984). This antinociceptive system can be engaged by aversive environmental stimuli, such as shock and restraint (Madden et al 1977;Terman et al 1984;Tricklebank and Curzon 1984). In the case of shock and other localized noxious stimuli, the antinociception is correlated with the inhibition of nociceptive neurons within the spinal cord and occurs in areas distant from the stimulation site (Morgan and Whitney 1996).…”