Effects of Ultrasound and Diclofenac Phonophoresis on Inflammatory Pain Relief: Suppression of Inducible Nitric Oxide Synthase in Arthritic Rats

Abstract

Abstract Background and Purpose. The direct effects of ultrasound (US) and phonophoresis of a nonsteroidal anti-inflammatory drug (NSAID) on injured peripheral tissue have been widely investigated, but evidence concerning the effects of central spinal nociceptive modulation seems to be lacking. The purpose of this study was to investigate the peripheral influences of US and phonophoresis on the modulation of spinal inducible nitric oxide synthase (iNOS) expression elicited by hind paw stimulation with an ankle injection of complete Freund adjuvant (CFA). Subjects and Methods. Inflammatory arthritis was induced in 18 male Wistar rats with intra-articular tibiotarsal injections of CFA. Serial changes in inflammatory pain reactions, including hind-limb edema, and the locomotor activity of the arthritic animals were measured. Arthritic rats underwent US (n=6), diclofenac phonophoresis (n=6), or sham treatment (n=6) on the CFA-injected leg at 18 hours after injection. At 20 hours after injection, spinal inducible nitric oxide synthase–like immunoreactive (iNOS-LI) cells were examined. Results. Following the CFA injection, all animals’ paw diameters and ankle circumferences ipsilateral to the injected leg were significantly increased compared with the values prior to injection. The rearing behavior of arthritic animals had improved significantly after US and diclofenac phonophoresis treatments. The mean total number (±SD) of iNOS-LI cells per section of segments L1 and L2 of the bilateral spinal cord of the sham treatment, US, and phonophoresis groups were 531.20±6.11, 124.20±4.09, and 114.80±3.23, respectively. The total numbers of iNOS-LI cells in rats treated with US and diclofenac phonophoresis were significantly smaller than in those receiving sham treatment. There were no significant differences in the total number of iNOS-LI cells ipsilateral to the injected leg between the US and diclofenac phonophoresis groups. Discussion and Conclusion. Ultrasound and phonophoresis treatments probably modulate and prevent the CFA-insult–induced increase in total and regional iNOS-LI neurons. Peripheral use of diclofenac phonophoresis offers little advantage over US alone in affecting the central mechanisms of nociception. The peripheral influences of US and phonophoresis on the central modulation of the spinal nociceptive processing system are important and may reflect the work being done through the neuroplasticity of spinal cord in response to peripheral input of US and phonophoresis. [Hsieh YL. Effects of ultrasound and diclofenac phonophoresis on inflammatory pain relief: suppression of inducible nitric oxide synthase in arthritic rats.]