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Antihyperalgesic effects of a novel muscarinic agonist ( LASSB io‐873) in spinal nerve ligation in rats
Author(s) -
Mendes Thaiana CF,
Antunes Fernanda,
Trachez Margarete M,
Nascimento Nailton M,
Fraga Carlos AM,
Barreiro Eliezer J,
ZapataSudo Gisele,
Sudo Roberto T
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12090
Subject(s) - medicine , neuropathic pain , pharmacology , analgesic , muscarinic acetylcholine receptor , agonist , methoctramine , hyperalgesia , anesthesia , allodynia , receptor , pirenzepine , nociception
Summary New chemicals or adjuvants with analgesic effects on chronic pain are needed and clinically relevant due to the limited number of effective compounds that possess these characteristics. LASSB io‐873, a pyrazolo[3,4‐ b ]pyrrolo[3,4‐ d ]pyridine derivative, activates muscarinic cholinergic receptors and has potent analgesic effects on acute and inflammatory pain. The present study evaluated the therapeutic and prophylactic effects of oral administration of LASSB io‐873 in a spinal nerve ligation ( SNL ) model of chronic peripheral nerve injury. LASSB io‐873 (100 mg/kg) inhibited the development of thermal hyperalgesia and mechanical allodynia when administered once daily for 7 consecutive days after SNL surgery and reversed these symptoms. LASSB io‐873 treatment did not alter rat behaviour in open field testing measured during the first 24 h after administration and again after 7 continuous days administration. The analgesic effect of LASSB io‐873 was inhibited by intrathecal methoctramine, an M 2 receptor antagonist, implicating the muscarininc M 2 receptor signalling pathway in the drug's action. These results reinforce the potential of LASSB io‐873 as a possible prototype for the development of more effective alternatives for the treatment of neuropathic pain.