Effect of tachykinin receptor antagonists in experimental neuropathic pain

The intrathecal effect of 0.1 to 10 microg of RP-67,580 (3aR,7aR)-7,7-diphenyl-2[1-imino-2(2-methoxyphenyl)-ethyl]++ +perhydroisoindol-4-one hydrochloride, CP-96,345 (2S,3S)-cis-(2(diphenylmethyl)-N-[(2-methoxyphenyl) methyl]-1-azabicyclo[2.2.2]octan-3-amine), SR-140,333 (S)-(1-¿2-[3-(3,4-dichlorophenyl)- 1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl¿-4-phenyl-1 -azonia-bicyclo[2.2.2.]-octane,chloride), all neurokinin (NK)1-receptor antagonists, SR-48,968 (S)-N-methyl-N[4-(4-acetylamino-4-[phenylpiperidino)-2-(3,4-dichlorophen yl)-butyl]benzamide, a tachykinin NK2 receptor antagonist and SR-142,801 (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)-N-methyl acetamide, a tachykinin NK3 receptor antagonist, and of their respective inactive enantiomers on thresholds of vocalization due to a mechanical stimulus in mononeuropathic (sciatic nerve ligature) and diabetic rats, was examined. The tachykinin NK1 and the NK2 receptor antagonists were antinociceptive in both models, with a higher effect of the former in diabetic rats. The tachykinin NK3 receptor antagonist was weakly effective in diabetic rats only. This indicates a differential involvement of the tachykinins according to the model of neuropathic pain, suggesting a potential role for tachykinin receptor antagonists in the treatment of neuropathic pain.