IN this issue of ANESTHESIOLOGY, Loftus et al. 1 report findings from a study examining the utility of ketamine as an adjunct analgesic in controlling postoperative pain. Is this just another report on the perioperative use of ketamine addressing a question that has already been answered? We know this works, right? Considering that the population under study consisted of patients on long-term o...

In all age groups, the use of opioids to treat chronic pain conditions has increased, yet the impact of age on opioid tolerance development has not been comprehensively addressed. In this study, we investigated age-related differences in morphine tolerance development in rats. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr were used in the study. Morphine (8 mg/kg) was injected subcutaneously twice each ...

The role of μ-opioid receptor (MOR) down-regulation in opioid tolerance remains controversial. In this study, we used a novel knock-in mouse to examine how changing the extent of MOR down-regulation alters the development of morphine tolerance. These mice express a mutant MOR, degrading MOR (DMOR), that differs from the wild-type (WT) MOR in two ways: 1) unlike the recycling WT MOR, the mutant ...

The opioid receptors (ORs) are known to be distributed widely in the central nervous system (CNS) and in peripheral sensory and autonomic nerves. Activation of ORs by endogenous and exogenous ligands results in a multitude of physiological functions and behaviors, e.g. pain and analgesia, stress and social status, tolerance and dependence, learning and memory, eating and drinking, and many more...

BACKGROUND Various methods exist for trialing patients for intrathecal drug delivery. Currently no standards exist regarding "best practices" for trialing techniques. OBJECTIVES The specific aim of the current study is to report results of patients trialed using a low-dose intrathecal morphine technique in the treatment of chronic noncancer pain. SETTING academic pain medicine practice ST...

Cancer pain is caused by continuous tissue injury, which may be due to surgery, infiltration of the surrounding organs including nerves, as well as from mucositis after chemoor radiotherapy. Nerve involvement, chronic opioid therapy and continuous nociceptive input cause hyperalgesia. Chronic stimulation of the dorsal root neurons leads to hyperalgesia and resistance (tolerance) to μ opioid ana...

Binding a critical pentapeptide region on the scaffolding protein filamin A regulates signaling of mu opioid receptors (MORs) so that their activation should not result in the opioid tolerance, dependence and addiction associated with current opioid painkillers. Additionally, we show that compounds that bind this site on filamin A reduce release of inflammatory cytokines. PTI-609 is a new chemi...

We have previously described novel cardioprotection in response to sustained morphine exposure, efficacious in young to aged myocardium and mechanistically distinct from conventional opioid or preconditioning (PC) responses. We further investigate opioid-dependent sustained ligand-activated preconditioning (SLP), assessing duration of protection, opioid receptor involvement, additivity with con...

Release of endogenous dynorphin opioids within the spinal cord after partial sciatic nerve ligation (pSNL) is known to contribute to the neuropathic pain processes. Using a phosphoselective antibody [kappa opioid receptor (KOR-P)] able to detect the serine 369 phosphorylated form of the KOR, we determined possible sites of dynorphin action within the spinal cord after pSNL. KOR-P immunoreactivi...