title: Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models.
abstract: Chemotherapy-induced neuropathies are widespread disorders evoked by characteristic damage of the nervous system. Sensory alterations, as paresthesia and dysesthesia, and severe pain are disabling side effects that altered quality of life, leading to therapy discontinuation. These kind of neuropathies are extremely difficult to treat and actual therapies are generally palliative. A great deal of interest has evolved around the relevance of nicotinic receptors as target for chronic pain therapy. Selective receptor subtype modulators have been described as active in pain relief. On the other hand, the profile of nicotine as such, or delivered by tobacco smoke, is a matter of debate since the analgesic properties may be impaired by receptor desensitization and tolerance. Nicotine acute effect on nociceptive threshold was evaluated in the Chronic Constriction Injury model in comparison with neuropathies induced by chemotherapeutic agents. Fourteen days after nerve injury, intraperitoneally administered nicotine (0.5-1.5 mg/kg) reduced hypersensitivity to noxious and non-noxious stimuli. Painful neuropathic state was alternatively established by the intravenously injection of the antiviral agent dideoxycytidine (25 mg/kg). Nicotine significantly reduced antiviral-dependent alterations of the nociceptive threshold. Moreover, nicotine decreased neuropathic pain induced by repeated intraperitoneal administration of the anticancer agent oxaliplatin (2.4 mg/kg), lowering the hypersensitivity to mechanical and thermal stimuli. In conclusion, intraperitoneal nicotine administration controls neuropathic pain evoked by traumatic or toxic nervous system alterations. These results support the nAChR modulation as a possible therapeutic approach to the complex, undertreated chemotherapy-induced neuropathies.
authors: Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. lorenzo.mannelli@unifi.it
authors: Lorenzo
authors: L
authors: Di Cesare Mannelli
authors: Matteo
authors: M
authors: Zanardelli
authors: Carla
authors: C
authors: Ghelardini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D000998:Antiviral Agents / Q000009:adverse effects; D003250:Constriction; D008297:Male; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000150:complications* / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000150:complications / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009538:Nicotine