μ but not δ and κ opioid receptor involvement in ventrolateral orbital cortex opioid-evoked antinociception in formalin test rats

Fish do not feel pain and its implications for understanding phenomenal consciousness

“…Morphine was only effective in inhibiting behaviours when connections between the forebrain and brainstem were left intact in sham-operated rats (Matthies and Franklin 1992). Moreover, local application of morphine into either the somatosensory, prefrontal orbital or agranular insular cortices attenuates behavioural responses in the formalin pain model in rats (Soto-Moyano et al 1988; Xie et al 2004). Thus, morphine is active in the rat forebrain, which is consistent with it modulating the subjective experience of the noxious stimuli, as in humans (Jones et al 1991; Taylor et al 2013).…”

“…Similarly, if an analgesic works at the level of the brainstem it can modulate both brainstem and higher-order brain responses (Pert and Yaksh 1975). If an analgesic is active at the level of the telencephalon and reduces behavioural responses (Xie et al 2004) then the animal, at least, has the possibility of feeling a noxious stimulus as painful (however this interpretation is dependent first, on the behaviour being non-reflexive and second, on the existence of the necessary neural hardware; see below). At present, the inference that fish feel pain because behavioural responses to noxious stimuli are attenuated following systemic administration of morphine (Sneddon 2003) is weak, particularly given that both the site of action as well as the physiological role of this drug in fish are unknown.…”

Engaging endogenous opioid circuits in pain affective processes

“…Preclinical work suggests that the OFC plays a role in opioid-mediated analgesia. Ventrolateral OFC infusion of morphine reduces mechanical and thermal allodynia and hypersensitivity in naive and chronic pain states (Huang et al, 2001;Zhao et al, 2007), and MOR activation in the ventrolateral OFC mediates the antinociceptive effect of morphine on rats experiencing formalin-induced hypersensitivity (Xie et al, 2004). The effect of morphine is reversed by naloxone (Huang et al, 2001), and blocked by a GABA A receptor antagonist (Qu et al, 2006), suggesting an opioid-induced decrease in GABAergic signaling underlies the behavioral effects of opiates in the OFC.…”

Advances in cortical modulation of pain

“…Moreover, pharmacological treatment of the VLO cortex with opioids (morphine), lidocaine, or GABA reduced levels of inflammatory pain in rodents, inhibited the tail-flick reflex and formalin-evoked c-Fos expression in the spinal cord, and suppressed thermal tactile allodynia and hyperalgesia 47,60,61. These results provide evidence for the hypothesis that opioid-induced antinociception in the VLO cortex might be produced by opioids via the μ-opioid receptor subtype 1, which exerts inhibitory effects on GABAergic inhibitory neurons, resulting in disinhibition of VLO cortex projection neurons and leading to activation of the VLO–PAG brain-stem descending pain-control system to depress the nociceptive inputs at the trigeminal/spinal cord level.…”