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.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Di Cesare Mannelli L,Zanardelli M,Ghelardini Cdoi
10.1016/j.ejphar.2013.04.022subject
Has Abstractpub_date
2013-07-05 00:00:00pages
87-94issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(13)00327-0journal_volume
711pub_type
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journal_title:European journal of pharmacology
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