title: Analgesic treatment with pregabalin does not prevent persistent pain after peripheral nerve injury in the rat.
abstract: Reducing the risk of chronic postoperative pain through preventive analgesia is an attractive therapeutic concept. Because peripheral nerve lesions are a major cause of chronic pain after surgery, we tested in rats whether analgesic treatment with pregabalin (PGB) has the capacity to mitigate the development of persistent neuropathic pain-like behavior. Starting on the day of spared nerve injury or 1week later, we treated rats with a continuous intrathecal infusion of PGB (300 or 900μg/24hours) or vehicle for up to 28days. Rats receiving early PGB treatment had almost normal withdrawal thresholds for punctate mechanical stimuli and were clearly less sensitive to pinprick or cold stimulation. The responses to punctate mechanical and cold stimulation were still reduced for a brief period after the infusion was terminated, but the difference from vehicle-treated rats was minor. Essentially, the analgesic effect of PGB was limited to the duration of the infusion, whether analgesia started at the time of surgery or with a delay of 1week, independently of the length of the treatment. PGB did not suppress the activation of spinal microglia, indicating that analgesia alone does not eliminate certain pain mechanisms even if they depend, at least partially, on nociceptive input. Unexpectedly, intrathecal infusion of PGB did not inhibit the nerve injury-induced accumulation of its binding target, the voltage-gated calcium channel subunit α2δ1, at primary afferent terminals in the spinal cord. Interference with the synaptic trafficking of α2δ1 is not required to achieve analgesia with PGB.
authors.affiliation: Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, NY, USA Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA Department of Radiology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA Department of Neurology, Massachusetts General Hospital, Boston, MA, USA Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: John
authors.initials: J
authors.lastname: Whang
authors.forename: William T
authors.initials: WT
authors.lastname: Derry
authors.forename: Daniel
authors.initials: D
authors.lastname: Vardeh
authors.forename: Joachim
authors.initials: J
authors.lastname: Scholz
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D059350:Chronic Pain / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
keywords: Neuropathic pain; Postoperative pain; Pregabalin; Preventive analgesia