title: Local loperamide injection reduces mechanosensitivity of rat cutaneous, nociceptive C-fibers.
abstract: Loperamide reverses signs of mechanical hypersensitivity in an animal model of neuropathic pain suggesting that peripheral opioid receptors may be suitable targets for the treatment of neuropathic pain. Since little is known about loperamide effects on the responsiveness of primary afferent nerve fibers, in vivo electrophysiological recordings from unmyelinated afferents innervating the glabrous skin of the hind paw were performed in rats with an L5 spinal nerve lesion or sham surgery. Mechanical threshold and responsiveness to suprathreshold stimulation were tested before and after loperamide (1.25, 2.5 and 5 µg in 10 µl) or vehicle injection into the cutaneous receptive field. Loperamide dose-dependently decreased mechanosensitivity in unmyelinated afferents of nerve-injured and sham animals, and this effect was not blocked by naloxone pretreatment. We then investigated loperamide effects on nerve conduction by recording compound action potentials in vitro during incubation of the sciatic nerve with increasing loperamide concentrations. Loperamide dose-dependently decreased compound action potentials of myelinated and unmyelinated fibers (ED50 = 8 and 4 µg/10 µl, respectively). This blockade was not prevented by pre-incubation with naloxone. These results suggest that loperamide reversal of behavioral signs of neuropathic pain may be mediated, at least in part, by mechanisms independent of opioid receptors, most probably by local anesthetic actions.
authors: Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America. platelet@jhmi.edu
authors: Matthias
authors: M
authors: Ringkamp
authors: Michael
authors: M
authors: Tal
authors: Timothy V
authors: TV
authors: Hartke
authors: Matthew
authors: M
authors: Wooten
authors: Alvin
authors: A
authors: McKelvy
authors: Brian P
authors: BP
authors: Turnquist
authors: Yun
authors: Y
authors: Guan
authors: Richard A
authors: RA
authors: Meyer
authors: Srinivasa N
authors: SN
authors: Raja
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D007267:Injections; D008139:Loperamide / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D055595:Mechanical Phenomena; D009412:Nerve Fibers / Q000187:drug effects* / Q000473:pathology; D009437:Neuralgia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects* / Q000473:pathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation*
chemical_list: D000701:Analgesics, Opioid; D008139:Loperamide