Nerve injury, diabetes and
cancer therapies are often associated with
painful neuropathy. The mechanism underlying
neuropathic pain remains poorly understood. The current
therapies have limited efficacy and are associated with dose-limiting side effects. Compounds which act at
nicotinic acetylcholine receptors have also been reported to show antinociceptive activity. Among those,
tebanicline (ABT-594) a potent
nicotinic acetylcholine receptor agonist demonstrated
analgesic effects across a broad range of preclinical models of nociceptive and
neuropathic pain. Another
nicotinic acetylcholine receptor agonist, 5-[(1R,5S)-3,6-Diazabicyclo[3.2.0]heptan-6-yl]nicotinonitrile (A-366833) from the same group produced significant antinociceptive effects in writhing
pain (abdominal constriction), acute thermal
pain (hot box), persistent chemical
pain (
formalin induced) and
neuropathic pain. In the present study, we have demonstrated the efficacy of
A-366833 in rat models of chronic constriction injury, partial sciatic nerve
ligation, spinal nerve
ligation, diabetes,
chemotherapy induced
neuropathic pain and complete
Freund's adjuvant induced inflammatory
pain.
A-366833 (1, 3 and 6 mg/kg) produced significant antihyperalgesic effects in partial sciatic nerve
ligation, chronic constriction injury and spinal nerve
ligation models. In the diabetic and
chemotherapy induced neuropathic models compound exerted antinociceptive activity and reduction in the
mechanical hyperalgesia was observed.
A-366833 dose dependently attenuated
mechanical hyperalgesia in complete
Freund's adjuvant induced inflammatory
pain model. These results demonstrated broad-spectrum antinociceptive properties of
A-366833 in both neuropathic and inflammatory
pain models.