Lack of evidence for increased descending inhibition on the dorsal horn of the rat following periaqueductal grey morphine microinjections

Abstract

1 Recordings were made from 18 neurones in the dorsal horn of the rat, anaesthetized with halothane. All cells received A-and C-fibre inputs and responded to innocuous and noxious stimuli applied to their excitatory receptive fields located on the extremity of the ipsilateral hindpaw. Transcutaneous application of suprathreshold (mean 3.2T) 2 ms square-wave pulses to the centre of the receptive fields resulted in responses to A-and C-fibre activation being observed; a mean 32.4 ± 6.0 C-fibre latency spikes were evoked per stimulus.2 A high dose (20 pg) of morphine in 0.5 pli sterile saline, microinjected into the periaqueductal grey matter (PAG) had no effect on the C-fibre-evoked activity of thirteen cells (72%) and facilitated 5 neurones (28%). Microinjection sites covered most of the PAG particularly the caudal medioventral zone.3 A relatively high dose (6 mg kg-', i.v.) of systemic morphine chloride, sufficient to elicit the direct spinal action of the opiate, inhibited all 5 cells tested. 4 We conclude that there is little evidence that the supraspinal action of morphine includes increased descending controls and depression of dorsal horn neurones in the rat.

The Effect of Hydromorphone Therapy on Psychophysical Measurements of the Descending Inhibitory Pain Systems in Patients with Chronic Radicular Pain

“…Regardless of that, the present study's findings, as well as several others [19–21,28], suggest that CPM might not be mediated by opioid‐related mechanisms but rather point to the involvement of other, non‐opioid mechanisms in CPM. The results of a recent study, which demonstrated CPM attenuation by the serotonin and neurepinephrine reuptake inhibitor deloxutine in patients with painful diabetic neuropathy [30], support this possibility.…”

“…The lack of effect of opioids on CPM is supported by an animal study that showed that microinjection of morphine into the PAG of rats did not enhance descending inhibition on the dorsal horn in rats. The authors concluded that “there is little evidence that the supraspinal action of morphine includes increased descending controls and depression of dorsal horn neurons” [28]. In contrast, other human studies demonstrated that opioids do have effects on CPM but in contradicting directions: In one such report, Le Bars et al.…”

Descending control of pain

“…Local microinjections of morphine at supraspinal sites have complex and variable actions on dorsal horn cell activity [17]. For example, microinjection into the PAG may inhibit, enhance or not affect responses to noxious stimulation in the dorsal horn [29,55]. One explanation of this may be the complexity of the organization of the PAG, as has been elegantly demonstrated in the work of Bandler and Shipley [8].…”

Opioid Receptors and Their Relevance to Anaesthesia

“…There is contradictory evidence that morphine both enhances and inhibits descending inhibitory control of spinal nociceptive pathways (e.g. [1,15,24,26]). Authors on both sides of the divide have produced interesting hypotheses as to how their findings might explain observations concerning the analgesic action of morphine.…”