Activation of the opioid and nonopioid hypoalgesic systems at the level of the brainstem and spinal cord: Does a coulometric relation predict the emergence or form of environmentally induced hypoalgesia?

Abstract

Prior research suggests that a coulometric relation (Intensity x Duration) determines whether an opioid or nonopioid hypoalgesic system is activated by afferent nociceptive information. Using a paradigm that generates a brainstem-mediated hypoalgesia on the tail-flick test, we found that a coulometric relation does not predict either the emergence or the form of shock-induced hypoalgesia in decerebrate rats. In fact, no evidence was obtained that the brainstem's opioid hypoalgesic system can be activated by ascending neurons. More severe shocks elicited hypoalgesia in spinalized rats. Although a coulometric relation did not predict the emergence of hypoalgesia in spinalized rats, shock severity did predict the form of the hypoalgesia; the least severe shocks elicited an opioid hypoalgesia, and the more severe shocks generated a nonopioid hypoalgesia. A similar pattern of data was observed in intact rats exposed to the least severe shock parameters.

The impact of morphine after a spinal cord injury

“…Separate groups received nothing (0 s) or 30 min of uncontrollable, intermittent tailshock. The shocks were 1.5 mA, 0.08 s in duration, and occurred on a variable time schedule (range 0.2 to 3.8 s) with a mean interstimulus interval of 2.0 s. (Shock at an intensity of 1.5 mA [AC, constant current] is known to engage antinociceptive mechanisms within the spinal cord [18,19], vigorous defensive behavior in intact rats, and pain in humans [see 8,9].) An experimenter blind to the subject's drug treatment recorded whether the shocked rats vocalized during the first minute of stimulation.…”

Stress-induced analgesia

“…As Millan (2002) points out in his extensive review of the descending control of pain, the difference in the mechanisms of facilitation and inhibition of nociception are primarily in receptor subtypes coupled to differing intracellular mechanisms. Spinal pathways, through mechanisms elaborated from the gate-control theory, and supraspinal descending inhibitory pain pathways, both play a role in mediating SIA (Grau, 1987;Grau et al, 1990;Madden et al, 1977;Meagher et al, 1993;Meagher et al, 1990;Rhudy et al, 2004;. Nociceptive information is then relayed either directly to the cortex or indirectly to the cortex through the brainstem, midbrain, and thalamus via the ascending pain pathways (for review see Millan, 1999).…”

Pain and negative affect: evidence the inverse benzodiazepine agonist DMCM inhibits pain and learning in rats

“…Prior parametric studies have shown that these three modes of defense can be sequentially engaged by increasing shock severity (duration, intensity, and/or density; Fanselow and Lester 1988;Meagher et al in review), and rely on distinct neural systems (Meagher et al 1993;Fanselow 1994;Grau et al 1996;Crown et al 2000). Following Fanselow (1994), we assumed that these distinct modes of defense can likewise be sequentially engaged by different levels of negative affect.…”