Functional relationship between brainstem putative pain-facilitating neurons and spinal nociceptfive neurons during development of inflammation in rats.

The so-called on- and off-cells of the rostral ventromedial medulla (RVM) send their axons to the spinal dorsal horn. Activation of on-cells precedes and coincides with a facilitation, and activation of off-cells coincides with an inhibition, of withdrawal reflexes elicited by noxious agents. Considerable evidence supports the notion that on- and off-cells modulate nocifensive reflexes during opioid and non-opioid action and also during normal circumstances and during peripheral neuropathy and inflammation. Yet it is unclear whether on- and off-cells act upon sensory spinal circuits that might lead to ascending projections and the experience of pain. Here, in deeply anesthetized rats we recorded single unit discharges from pairs of one on-like or off-like cell in RVM and a nociceptive neuron in the spinal dorsal horn with input from a hind paw. Both ongoing activity and responses to a calibrated noxious stimulus applied to the paw were documented during basal conditions and during development of paw inflammation. Probably due to the strong barbiturate anesthesia, off-like cells were depressed and did not yield interpretable results. However, we showed for the first time that during the increase in neuronal activity that results from paw inflammation the activity of spinal nociceptive neurons reflects the activity of their partner on-like cells in a highly correlated manner. This implies a tight relationship between spinal sensory and RVM modulatory functions that may underlie inflammation-induced hyperreflexia and clinically relevant hyperalgesia.