BACKGROUND Tolerance is defined as a phenomenon in which exposure to a drug results in a decrease of an effect or the requirement of a higher dose to maintain an effect. The fear of a patient developing opioid tolerance contributes regularly to the stigmatization and withholding of intrathecal opioid therapy for chronic pain of non-cancer origin. OBJECTIVES The aim of this study was to descri...

BACKGROUND In 2006, the authors observed a cluster of three deaths, which circumstances suggested were opioid-related, within 1 day after placement of intrathecal opioid pumps for noncancer pain. Further investigation suggested that mortality among such patients was higher than previously appreciated. The authors performed investigations to quantify that mortality and compare the results to con...

BACKGROUND Selective inhibitors of cyclooxygenase (COX)-2 are commonly used analgesics in various pain conditions. Although their actions are largely thought to be mediated by the blockade of prostaglandin (PG) biosynthesis, evidences suggesting endogenous opioid peptide link in spinal antinociception of COX inhibitor have been reported. We investigated the roles of opioid receptor subtypes in ...

In a recent Ethics Forum [1], Drs. John Loeser and Tim Deer opined on a case study involving the question of whether a patient should be considered for the implantation of an intrathecal opioid pump. While Dr. Loeser, who has been a critic of intrathecal opioids, recommended against implantation, Dr. Deer surprised many readers by also questioning the prudence of implantation in this particular...

The present study was performed to explore the modulatory potential of different endogenous opioid systems on transmission of presumed nociceptive information at the spinal cord level in thermally injured rats. Thermal injury was performed by dipping the left paw into water 60 degrees C for 20 s. This induced a significant bilateral decrease in hindpaw withdrawal latency HWL to pressure. Intrat...

BACKGROUND The pivotal role of glial activation and up-regulated inflammatory mediators in the opioid tolerance has been confirmed in rodents but not yet in humans. Here, the authors investigated the intraspinal cytokine and chemokine profiles of opioid-tolerant cancer patients; and to determine if up-regulated chemokines could modify opioid tolerance in rats. METHODS Cerebrospinal fluid samp...

Morphine has been widely used as rescue treatment for heart attack and failure in humans for many decades. Relatively little has been known about the role of spinal opioid receptors in morphine cardioprotection. Recent studies have shown that intrathecal injection of morphine can reduce the heart injury caused by ischemia (I)/reperfusion (R) in rats. However, the molecular and cellular mechanis...

BACKGROUND Intrathecal opioid administration has been used widely in patients suffering from severe cancer pain that is not managed with conventional modalities. However, the potential serious neurological complications from the procedure and the side effects of intrathecal opioids have made many clinicians reluctant to employ continuous intrathecal analgesia as a first-line therapeutic option ...

Intrathecal (i.t.) pretreatment with a low dose (0.3 nmol) of morphine causes an attenuation of i.t. morphine-produced analgesia; the phenomenon has been defined as morphine-induced antianalgesia. The opioid-produced analgesia was measured with the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with low dose (0.3 nmol) of morphine time dependently attenuated i.t. morphine-prod...

UNLABELLED The management of pain due to cancer is challenging and often requires invasive therapy in addition to medication management. Intrathecal drug delivery is a form of advanced therapy that delivers medication locally in the intrathecal space while reducing systemic side effects associated with high doses of opioids. Although risks associated with intrathecal drug delivery are low, some...