Chronic pain is a prevalent and debilitating condition, conveying immense human burden. Suffering from chronic pain is not only caused by painful symptomatology, but also through a wide range of psychopathological and physical consequences, including depression and anxiety disorders, impaired sleep and cognition, cardiovascular morbidity and impaired sexual function, all contributing to diminis...

BACKGROUND Opioid misuse and abuse occurring in association with the treatment of chronic non-cancer pain are not new phenomena, but their increasing prevalence in recent years is unprecedented. Advancements in pharmaceutical technologies have provided opioid-related drugs, which lack the pure mu agonist activity characteristic of the typical opioid congeners. This absent or altered mu receptor...

INTRODUCTION The use of chronic opioid therapy for chronic non-cancer pain is growing and is now accepted as an effective treatment modality. AREAS COVERED Although there are guidelines and reviews for chronic opioid therapy for chronic non-cancer pain patients, physicians may still have concerns and be reluctant to prescribe strong opioids for chronic non-cancer pain. Common issues and conce...

Introduction: Sex differences are observed in the development of tolerance to antinociceptive effect of opioid drugs such as morphine, but the underlying mechanisms remain unclear. Critical role of glutamate in the development and maintenance of opioid tolerance has been reported by many investigators. There are also evidences about interaction between gonadal hormones and neuromodulatory sy...

1 An intrathecal (i.t.) injection of a selective d2-opioid receptor agonist, [D-Ala]deltorphin II, produced an acute antinociceptive tolerance to the antinociceptive e€ect of a subsequent i.t. challenge of [DAla]deltorphin II. This acute tolerance lasted 3 to 9 h and completely subsided by 12 h. The experiments were designed to examine the e€ect of pretreatment with an antisense oligodeoxynucle...

Opioid-induced proinflammatory glial activation modulates wide-ranging aspects of opioid pharmacology including: opposition of acute and chronic opioid analgesia, opioid analgesic tolerance, opioid-induced hyperalgesia, development of opioid dependence, opioid reward, and opioid respiratory depression. However, the mechanism(s) contributing to opioid-induced proinflammatory actions remains unre...

Treatment of pain with morphine and its congeners in sickle cell anemia is suboptimal, warranting the need for analgesics devoid of side effects, addiction and tolerance liability. Small-molecule nociceptin opioid receptor ligands show analgesic efficacy in acute and chronic pain models. We show that AT-200, a high affinity nociceptin opioid receptor agonist with low efficacy at the mu opioid r...

BACKGROUND Opioids have become the mainstay for treatment of moderate to severe pain and are commonly used to treat surgical pain. While opioid administration has been shown to cause opioid-induced hyperalgesia and tolerance, interactions between opioid administration and surgery with respect to these problematic adaptations have scarcely been addressed. Accumulating evidence suggests opioids a...

We have previously described a cyclic tetrapeptide, 1, that displays μ opioid receptor (MOPr) agonist and δ opioid receptor (DOPr) antagonist activity, a profile associated with a reduced incidence of opioid tolerance and dependence. Like many peptides, 1 has poor bioavailability. We describe here an analogue of 1 with an added C-terminal β-glucosylserine residue, Ser(β-Glc)NH2, a modification ...