Kappa Opioid Receptor Distribution and Function in Primary Afferents.

This is an interesting study confirming analgesic effects mediated by peripheral kappa opioid receptors (KOR). One of the authors’ findings is that peripherally-restricted KOR agonists attenuate paw incision-induced mechanical, but not heat sensitivity. That peripherally-acting opioids are particularly effective against mechanical pain has been observed previously. For example, we found that activation of peripheral KOR (as well as mu- and delta-opioid receptors) in injured nerves was more effective in amelioration of mechanical than heat sensitivity in the chronic constriction injury-induced neuropathic pain model in mice. Nevertheless, heat sensitivity was also diminished, providing that opioids were injected at higher, but still peripherally-acting doses (Labuz and Machelska, 2013). Thus, the conclusion that peripherally-restricted KOR agonists fail to influence heat sensitivity, based on testing the agonists at only one dose, appears premature. Dose-response experiments and verification of the peripheral action site would be required to make a definitive conclusion.