Blockade of opioid receptors in rostral ventral medulla prevents antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS)

Although transcutaneous electrical nerve stimulation (TENS) is used extensi vely in inflammatory joint conditions such as arthritis, the underlying mec hanisms are unclear. This study aims to demonstrate an opiate-mediated acti vation of descending inhibitory pathways from the rostral ventral medulla ( RVM) in the antihyperalgesia produced by low- (4 Hz) or high-frequency (100 Hz) TENS. Paw withdrawal latency to radiant heat, as an index of secondary hyperalgesia, was recorded before and after knee joint inflammation (induc ed by intra-articular injection of 3% kaolin and carrageenan) and after TEN S/no TENS coadministered with naloxone (20 mug/1 mul), naltrindole (5 mug/1 mul), or vehicle (1 mul) microinjected into the RVM. The selectivity of na loxone and naltrindole doses was tested against the mu -opioid receptor ago nist [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO) (20 ng, 1 mul) and the delta (2)-opioid receptor agonist deltorphin (5 mug, 1 mul) in the RVM . Naloxone microinjection into the RVM blocks the antihyperalgesia produced by low frequency (p < 0.001), but not that produced by high-frequency TENS (p>0.05). In contrast, naltrindole injection into the RVM blocks the antih yperalgesia produced by high-frequency (p< 0.05), but not low-frequency (p > 0.05) TENS. The analgesia produced by DAMGO and deltorphin is selectively blocked by naloxone (p < 0.05) and naltrindole (p < 0.05), respectively. T hus, the dose of naloxone and naltrindole used in the current study blocks mu- and delta -opioid receptors, respectively. Hence, low-frequency and hig h-frequency TENS produces antihyperalgesia by activation of mu- and delta - opioid receptors, respectively, in the RVM.