Abstract | BACKGROUND:
Opioids have long been regarded as the most effective drugs for the treatment of severe acute and chronic pain. Unfortunately, their therapeutic efficacy and clinical utility have been limited because of central and peripheral side effects. METHODS: RESULTS:
DALDA, administered subcutaneously, had 70 times greater efficacy for inhibiting thermal (n = 8 to 11/group) than mechanical hypersensitivity (n = 6 to 8/group) in male rats. The pain inhibitory effects of DALDA on mechanical and heat hypersensitivity were abolished in animals pretreated with systemic methylnaltrexone (n = 7 to 9/group), a peripheral μ- opioid receptor antagonist. In the spinal wide-dynamic range neurons, systemic DALDA inhibited C-fiber-mediated, but not A-fiber-mediated, response in neuropathic male rats (n = 13). In primary sensory neurons, DALDA inhibited the capsaicin-induced [Ca2+] increase more than the β- alanine-induced [Ca] increase (n = 300); capsaicin and β- alanine activate subpopulations of neurons involved in the signaling of heat and mechanical pain, respectively. DALDA-treated rats (n = 5 to 8/group) did not exhibit motor deficits and locomotor impairment suggesting that it does not induce central side effects. CONCLUSIONS: These findings suggest that DALDA may represent a potential alternative to current opioid therapy for the treatment of neuropathic pain and is likely to be associated with minimal adverse effects.
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Authors | Vinod Tiwari, Fei Yang, Shao-Qiu He, Ronen Shechter, Chen Zhang, Bin Shu, Tong Zhang, Vineeta Tiwari, Yun Wang, Xinzhong Dong, Yun Guan, Srinivasa N Raja |
Journal | Anesthesiology
(Anesthesiology)
Vol. 124
Issue 3
Pg. 706-20
(Mar 2016)
ISSN: 1528-1175 [Electronic] United States |
PMID | 26756519
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics, Opioid
- Opioid Peptides
- Receptors, Opioid, mu
- dermorphin
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Topics |
- Analgesics, Opioid
(therapeutic use)
- Animals
- Female
- Male
- Neuralgia
(drug therapy, metabolism)
- Opioid Peptides
(pharmacology, therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Receptors, Opioid, mu
(agonists, metabolism)
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