Injectable Capsaicin for the Management of Pain Due to Osteoarthritis.

Capsaicin is a potent agonist of the TRPV1 channel, a transduction channel that is highly expressed in nociceptive fibers (pain fibers) throughout the peripheral nervous system. Given the importance of TRPV1 as one of several transduction channels in nociceptive fibers, much research has been focused on the potential therapeutic benefits of using TRPV1 antagonists for the management of pain. However, an antagonist has two limitations. First, an antagonist in principle generally only affects one receptor. Secondly, most antagonists must have an ongoing presence on the receptor to have an effect. Capsaicin overcomes both liabilities by disrupting peripheral terminals of nociceptive fibers that express TRPV1, and thereby affects all of the potential means of activating that pain fiber (not just TRPV1 function). This disruptive effect is dependent on the dose and can occur within minutes. Thus, unlike a typical receptor antagonist, continued bioavailability at the level of the receptor is not necessary. By disrupting the entire terminal of the TRPV1-expressing nociceptive fiber, capsaicin blocks all the activation mechanisms within that fiber, and not just TRPV1 function. Topical capsaicin, an FDA approved treatment for neuropathic pain, addresses pain from abnormal nociceptor activity in the superficial layers of the skin. Effects after a single administration are evident over a period of weeks to months, but in time are fully reversible. This review focuses on the rationale for using capsaicin by injection for painful conditions such as osteoarthritis (OA) and provides an update on studies completed to date.

Antinociceptive and side-effects of hydromorphone after subcutaneous administration in cats.

The subcutaneous (SC) route is often chosen for drug administration in cats because it is easier to perform than intravenous (IV) injection and is perceived as less painful than intramuscular (IM) injection. However, little is known of how the route of administration influences the pharmacodynamics of drugs. This study measured the changes in skin temperature and thermal threshold (TT) and recorded the side-effects after SC injection of 0.1mg/kg of hydromorphone in six cats. Time to peak TT was 105min. Skin temperature was elevated at 15min and between 45 and 360min. Five cats vomited and two exhibited marked dysphoria. Compared to previously published studies of IV and IM administration of hydromorphone, the SC route results in a slower onset of peak effect, a shorter duration of antinociception and is associated with more undesirable side-effects. As with IV and IM injections, SC administration of hydromorphone at 0.1mg/kg is associated with a significant elevation in skin temperature. Overall, the SC route appears to have the least utility.