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Antinociceptive effects of NCX‐701 (nitro‐paracetamol) in neuropathic rats: enhancement of antinociception by co‐administration with gabapentin
Author(s) -
CurrosCriado M Mar,
Herrero Juan F
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00343.x
Subject(s) - nociception , gabapentin , neuropathic pain , pharmacology , stimulation , spinal cord , medicine , noxious stimulus , analgesic , anesthesia , chemistry , receptor , alternative medicine , pathology , psychiatry
Background and purpose: Neuropathic pain is characterized by a poor response to classic analgesics. In the present study, we have assessed the antinociceptive activity of NCX‐701 (nitro‐paracetamol) in neuropathic rats, after systemic and intrathecal (i.t.) administration. In addition, we analysed the possible benefit of the combination of NCX‐701 and gabapentin, a well‐known potent analgesic, in the treatment of neuropathic pain Experimental approach: The antinociceptive effects of i.v. and i.t. NCX‐701 and paracetamol were studied in spinal cord neuronal responses from neuropathic adult male Wistar rats, using the recording of single motor units technique. The effect of i.v. and i.t. NCX‐701 in combination with i.v. gabapentin was studied by isobolographic analysis. Key results: The experiments showed that NCX‐701, but not paracetamol, dose‐dependently reduced the nociceptive responses evoked by noxious mechanical and electrical stimulation, after i.v. (ID 50 542 ± 5 µmol·kg −1 for noxious mechanical stimulation) or i.t. (ID 50 932 ± 16 nmol·kg −1 ) administration. The combined administration of i.v. or i.t. NCX‐701 and i.v. gabapentin induced a more intense antinociceptive effect than any of the two drugs given alone. The isobolographic analysis showed a synergistic effect. Conclusions and implications: NCX‐701 is an effective antinociceptive compound in situations of neuropathy‐induced sensitization, with an action mainly located in the spinal cord. The combination of NCX‐701 and gabapentin induces a synergistic enhancement of the depression of nociceptive responses evoked by natural noxious stimulation. The use of NCX‐701 alone or in combination with gabapentin might open up new and promising perspectives in the treatment of neuropathic pain.