Khasabov SG, Fliss PM, Rao AS, Simone DA (2010) NK-1 Receptors in the RVM: Involvement in hyperalgesia produced by naloxone but not in morphine analgesia. Neuroscience 2010 Abstracts 678.15/QQ2. Society for Neuroscience, San Diego, CA.
Summary: The rostral ventromedial medulla (RVM) is a crucial supraspinal site for opioid analgesia. Descending modulation of nociceptive transmission by the RVM can be antinociceptive, which is associated with increased activity of OFF cells, or pronociceptive, which is related to activation of ON cells. Analgesia produced by opioids at the RVM level is due to direct inhibition of ON cells and the indirect increase in discharge of OFF cells. A subpopulation of neurons in the RVM (approximately 7%) express neurokinin-1 receptors (NK-1R), which are receptors for substance P (SP). We have shown that NK-1R in the RVM are located primarily on ON cells and contribute to descending facilitation of nociception. We suggest that elimination of NK-1R expressing neurons by the specific saporin toxin conjugate SSP-SAP, will reduce the number of ON cells and thereby decrease descending facilitation without affecting antinociception associated with activity of OFF cells. We therefore determined the contribution of NK-1R expressing neurons in the RVM to changes in nocifensive behaviors produced by morphine or the opioid receptor antagonist naloxone by eliminating NK-1R expressing neurons. Adult male Sprague Dawley rats were pretreated with injection of SSP-SAP (1 µM/0.5 µl) or inactive toxin into the RVM. Ablation of NK-1R possessing neurons was determined histologically and did not alter tale flick or paw withdrawal latencies to heat for up to 4 weeks following treatment, indicating that these neurons do not modulate acute nociception. Morphine (30 µg/0.5 µl) injected into the RVM of control rats or rats pretreated with SSP-SAP increased tail flick latencies approximately 133.5 ± 20.8% and 140.4 ± 8.3%, respectively. The increase in paw withdrawal latency following morphine was also similar between groups. However, injection of naloxone (50 µg/0.5 µl) in control rats decreased tail flick latencies for 90 min with a maximal reduction of 32.2 ± 4.1%, whereas in rats treated with SSP-SAP latencies decreased by 17.8 ± 4.9% and for only 30 min. A similar pattern of effects was found on paw withdrawal latencies to heat. These data support the notion that ON cells possess NK-1Rs and contribute to facilitation of nociceptive transmission.
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