Nefopam has a pharmacologic profile distinct from that of opioids or other anti-inflammatory drugs. Several recent studies demonstrate that nefopam has a mechanism of action similar to those of anti-depressants and anticonvulsants for treating neuropathic pain. The present study investigates the mechanical antiallodynic effect of nefopam using immunohistochemical study and western blot analysis in a rat neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve ligation and intrathecal catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the sham surgery group (group S). Nefopam, either 10 or 100 microg/kg (group N10 or N100, respectively), and normal saline (group C) were intrathecally administered into the catheter every day for 14 days. The mechanical allodynic threshold of intrathecal nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5. Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic adenosine monophosphate response element binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal nefopam reduced mechanical allodynia in a rat neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the transcription factors' mitogen-activated protein kinases in the spinal cord.
Analgesics, Non-Narcotic/administration & dosage ; Animals ; Dose-Response Relationship, Drug ; Hyperalgesia/*drug therapy/etiology/*physiopathology ; Injections, Spinal ; Male ; Nefopam/*administration & dosage ; Neuralgia/complications/*drug therapy/*physiopathology ; Pain Measurement/drug effects ; Pain Perception/*drug effects ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome

The investigation was aimed to determine prognostic factors related to postherpetic neuralgia (PHN), and treatment options for preventing PHN. The data showed 34 (17.0%) out of 188 patients with herpes zoster had severe pain after 4 weeks, and 22 (11.7%) after 8 weeks, compared with 109 (58.0%) at presentation. The age (>or=50 yr), surface area involved (>or=9%), and duration of severe pain (>or=4 weeks) might be the main factors that lead to PHN. On the other hand, gender, dermatomal distribution, accompanied systemic conditions, and interval between initial pain and initiation of treatment might not be implicated in PHN. The subjects were orally received antiviral (valacyclovir), tricyclic antidepressant (amitriptyline), and analgesic (ibuprofen) as the standard treatment in the group 1. In addition to the standard medication, lidocaine solution was sub- and/or perilesionally injected in the group 2, while lidocaine plus prilocaine cream was topically applied to the skin lesions in the group 3. The rates of PHN in the 3 treatment groups were not significantly different, suggesting adjuvant anesthetics may not be helpful to reduce the severity of pain.
Acyclovir/administration & dosage/*analogs & derivatives ; Adolescent ; Adult ; Aged ; Amitriptyline/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Antidepressive Agents, Tricyclic/administration & dosage ; Antiviral Agents/administration & dosage ; Child ; Drug Therapy, Combination ; Female ; Herpes Zoster/*complications/drug therapy/physiopathology ; Humans ; Ibuprofen/administration & dosage ; Male ; Middle Aged ; Neuralgia/drug therapy/*etiology/physiopathology/prevention & control ; Prognosis ; Time Factors ; Valine/administration & dosage/*analogs & derivatives