BLOCKADE OF MU-OPIOID RECEPTORS IN THE ROSTRAL VENTRAL MEDULLA (RVM) PREVENTS ANTIHYPERALGESIA PRODUCED BY LOW FREQUENCY BUT NOT HIGH FREQUENCY TENS

A B Kalra; M O Urban; K A Sluka

PURPOSE: Although TENS is used extensively for pain relief in musculoskeletal conditions including inflammatory joint conditions like arthritis, the underlying mechanisms are unclear. This study aims to demonstrate an opiate mediated activation of descending inhibitory pathways in rostral ventral medulla (RVM) in the anti-hyperalgesia produced by low (4 Hz) or high frequency (100 Hz) TENS. SUBJECTS: An animal model (36 male Sprague Dawley rats) of inflammation (3%kaolin / 3% carrageenan into the knee joint) was used in this study. METHODS AND MATERIALS: Hyperalgesia was determined by measuring the paw withdrawal latency (PWL) to radiant heat. [micro]-opioid receptors were blocked by microinjection of naloxone into the RVM through a guide cannula implanted 3-5 days prior. Saline was microinjected into the RVM as a control. Measurements were taken: 1) before inflammation, 2) after inflammation and 3) post TENS (or no TENS) plus naloxone (1 [micro]l, 20 [micro]g) or saline (1 [micro]l). The selectivity of the naloxone dose used was tested against a selective [micro]-opioid receptor agonist (DAMGO; 1 [micro]l, 20ng) (n =4) and a selective [Delta]--opioid receptor agonist (SNC80; 1 [micro]l, 0.2 [micro]g), (n =4) microinjected into the RVM. PWL to radiant heat was assessed before and after DAMGO or SNC80, and after DAMGO+ naloxone or SNC80+ naloxone. ANALYSES AND RESULTS: The PWL was converted to percent inhibition with the following formula: % Inhibition = (Post TENS PWL -Post inflammation PWL) / (Baseline PWL-Post inflammation latency) (*)100. Data is presented as mean [+ or -] SEM. One-way ANOVA assessed group effects for percent inhibition of TENS. DAMGO (P=0.004) (paired t-test), or SNC80 (P=0.01) (paired t-test) injected into the RVM increased the PWL by 4-6s above baseline. Naloxone blocked the analgesia produced by DAMGO (P = 0.007) but not SNC80 (P= 0.43). Naloxone injection into the RVM blocked the antihyperalgesia produced by low-frequency TENS (P =0.04), but not that produced by high frequency TENS (P=0.10). CONCLUSIONS: The dose of naloxone utilized in the current study selectively blocks [micro]-opioid receptors. Hence low frequency TENS produces antihyperalgesia by activation of [micro]-opiate receptors in the RVM. Supported by the Arthritis Foundation, TENS units provided by EMPI, INC.

BLOCKADE OF MU-OPIOID RECEPTORS IN THE ROSTRAL VENTRAL MEDULLA (RVM) PREVENTS ANTIHYPERALGESIA PRODUCED BY LOW FREQUENCY BUT NOT HIGH FREQUENCY TENS

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