A. Kalra et al., Blockade of opioid receptors in rostral ventral medulla prevents antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS), J PHARM EXP, 298(1), 2001, pp. 257-263
Citations number
48
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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.