<b>TRPV1 channels induce Knee osteoarthritis pain: <i>in vivo</i> patch–clamp analysis</b>

Abstract

Osteoarthritis (OA) of knee is a common disease in the elderly, and these patients have severe knee pain as chief complaints. OA pain reduces ADL and QOL in these patients. The degree of pain does not correlate with radio­graphic grades, and the strong wear of cartilage does not mean necessarily strong pain. However, the cellular mechanism of chronic pain in this disease has been unclear. Recently many reports have suggested that transient receptor potential vanilloid 1 (TRPV1) is involved in various kinds of persistent pain, including knee OA pain. In this study to clarify the mechanisms underlying knee OA pain, we analyzed the nociceptive signals from the knee joint by recording spontaneous excitatory postsynaptic currents (sEPSC) in spinal dorsal horn neurons by in vivo patch–clamp technique. In order to generate knee OA model, Monosodium Iodoacetate (MIA) was injected into the right knee joint of male adult Sprague–Dawley rats. Three weeks after the injection of MIA, we performed in vivo patch–clamp recording from substantia gelatinosa (SG) neurons containing the L3–5 dorsal root entry zone. The average frequency of sEPSC in OA model rats was significantly larger than that of normal rats (p<0.05). Moreover, we analyzed sEPSC at each spinal segment in normal and OA rats. At L3 and L4 level the average frequency of sEPSCs in OA rats was significantly larger than that of normal rats. Next, we analyzed the effects of a TRPV1 antagonist, capsaicin injection into right knee of normal or OA rats. The capsaicin–induced increases of the frequency and amplitude of sEPSC were weak and had ended instantly in normal rats. While in OA model rats sEPSC largely increased immediately after capsaicin injection and it had lasted for a long time. This capsaicin–induce sEPSC enhancement was significantly larger than those in normal. These results suggest that TRPV1 is an important contributor to OA pain enhancement. And TRPV1 could be the target of pain relief in the patients suffering from the persistent knee OA pain.