title: Sensory neuron-specific receptor agonist BAM8-22 inhibits the development and expression of tolerance to morphine in rats.
abstract: We observed that intrathecal (i.t.) bovine adrenal medulla 22, an endogenous opioid peptide, partially reverses morphine tolerance. However, its mechanism remains unclear. The present study determined the effects of BAM8-22, a derivative of BAM22 and selective sensory neuron-specific receptor (SNSR) agonist, on the development and maintenance of tolerance to spinal morphine. Intrathecal administration of BAM8-22 at various doses (0.1, 1 and 10nmol) did not alter withdraw latencies assessed in both paw withdraw and tail flick tests. Co-administration of BAM8-22 (0.1nmol) every other day, but not daily, with morphine remarkably attenuated the development of morphine tolerance. Pretreatment and co-treatment with BAM8-22 (0.1nmol) significantly reversed established morphine tolerance. Furthermore, intermittent administration of BAM8-22 with morphine consistently resumed morphine-induced antinociception. However, i.t. BAM8-22 did not alter morphine-induced hyperalgesia. These results suggested that SNSR may be able to modulate the sensitivity of opioid receptor serving as a most probable underlying mechanism for the effects of BAM8-22 on morphine tolerance. This study also demonstrated that intermittent combination of SNSR agonist BAM8-22 with morphine might be better regimen for long-term use of opioids to treat chronic pain.
authors.affiliation: College of Life Sciences, Fujian Normal University, People's Republic of China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Cai
authors.forename: Jianping
authors.initials: J
authors.lastname: Jiang
authors.forename: Tingjun
authors.initials: T
authors.lastname: Chen
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Hong
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments; D011498:Protein Precursors / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*
chemical_list: D000700:Analgesics; D010446:Peptide Fragments; D011498:Protein Precursors; D043562:Receptors, G-Protein-Coupled; D004744:Enkephalin, Methionine; C028837:BAM 22P; D009020:Morphine