Transcutaneous Electrical Nerve Stimulation Reduces Knee Osteoarthritic Pain by Inhibiting Spinal Glial Cells in Rats

Abstract

Background. Transcutaneous electrical nerve stimulation (TENS) is commonly used for pain control. However, the effects of TENS on osteoarthritis (OA) pain and potential underlying mechanisms remain unclear. Objective. The objective of this study was to investigate the effect of TENS on OA pain treatment and underlying mechanisms related to glial cell inhibition. Design. This was an experimental study. Methods. OA was induced by injection of monosodium iodoacetate into the synovial space of the right knee joint of rats. High-frequency (HF) TENS (100 Hz), low-frequency (LF) TENS (4 Hz), or sham TENS was applied to the ipsilateral knee joint for 20 minutes. Paw withdrawal threshold (PWT), weight bearing, and knee bend score (KBS) were measured. Immunohistochemistry for microglia and astrocytes was performed with L3 to L5 spinal segment samples. To investigate the effects of glial inhibition on OA pain, minocycline, l-alpha-aminoadipate, or artificial cerebrospinal fluid was injected intrathecally, and PWT and KBS were measured. Results. Compared with sham TENS, both HF TENS and LF TENS significantly increased PWT, decreased KBS, and inhibited activated microglia in the L3 to L5 segments but did not decrease the total number of microglia, except in the L4 segment (HF TENS). Astrocyte expression was significantly decreased in the L3 to L5 segments following LF TENS and in the L3 segment following HF TENS. Compared with artificial cerebrospinal fluid, both minocycline and l-alpha-aminoadipate increased PWT and decreased KBS. Limitations. These results cannot be generalized to humans. Conclusions. TENS alleviates OA pain in rats by inhibiting activated microglia and reducing astrocyte expression in the spinal cord. Although these results may not be generalizable to chronic pain in patients with OA, within the limitation of the experimental animal model used in the present study, they suggest a possible mechanism and preclinical evidence supporting further experimentation or clinical use of TENS in humans.