Seminars in Pain Medicine最新文献

Use of the intrathecal route to deliver drugs has become an acceptable treatment method for difficult pain syndromes. The primary advantage of intrathecal administration is the ability to deliver adequate relief at substantially lower doses of medication compared with other routes. This reduction of drug dosing leads to fewer side effects and improved efficacy. Morphine sulfate has been the most commonly used drug although other opioids and nonopioids have been prescribed. Over the past decade, the complication of an inflammatory mass at the catheter tip has been described. The prevalence of this problem appears to be much lower than 1%; however, because of the potential hazards, diagnostic vigilance is critical. Patient evaluation and reevaluation are the most important part aspect of the diagnosis. Loss of clinical efficacy, dermatomal pain in the distribution of the catheter tip, proprioceptive change, and sensory loss are early warnings. Motor loss, bladder and bowel dysfunction, and paralysis are late findings and occur with progression. When suspicion of the complication arises, a plain film should be obtained to identify the catheter tip, and then a T₁-weighted image should be performed at the tip. When magnetic resonance imaging (MRI) is not possible, a computerized tomography (CT) myelogram is an acceptable alternative. Treatment of this lesion involves discontinuing the infusion, then revising or removing the catheter. If spinal cord compression occurs, the treatment is direct surgical decompression. Many patients have continued with treatment after an inflammatory mass is diagnosed, once the catheter is revised or replaced. Prevention includes change of medications, avoidance of high-concentration morphine and hydromorphone, change of catheter tip location, and use of multiorifice catheters.

Subarachnoidal and epidural are the two most frequent routes for intraspinal drug delivery in treatment of chronic pain and spasticity. In addition, there are less frequently used intraventricular and subdural routes. In this review, basic concepts of intraspinal drug delivery using different intraspinal routes are discussed. The intrathecal administration of drugs is preferred today, mainly because of effective dosing in low volumes using portable infusion systems. Intrathecal catheters are longer lasting and have lower rates of complications than epidural; there are fewer side effects and development of tolerance in patients with chronic pain is reduced when the intrathecal route is used. Today, for long-term pain management in patients with benign chronic pain and in those cancer patients with longer life expectancy, the intrathecal route is preferred.

Acute morphine withdrawal results in enhanced responsiveness to noxious stimulation in adult humans and rodents. This study extends these findings by demonstrating that acute morphine withdrawal produces allodynia in neonatal rats that is dependent on the translocation of protein kinase C ϵ and γ (ϵPKC and γPKC, respectively) in a developmentally specific manner. Basal expression of ϵPKC in dorsal root ganglia, and γPKC in lamina II of the lumbar spinal cord, were lower in postnatal day 7 (P7) compared with P21 rats. ϵPKC immunoreactivity increased in P7 rats at 4 hours after acute administration of morphine, whereas ϵPKC immunoreactivity decreased at 4 hours in P21 rats. In contrast to ϵPKC, there was a loss of γPKC immunoreactivity following morphine administration in both P7 and P21 rats. To determine whether ϵ and γPKC contribute to acute withdrawal-induced allodynia in neonatal rats, isozyme-specific inhibitors of ϵ and γPKC translocation were administered before or after morphine administration. Naloxone was used to precipitate withdrawal at either 30 or 120 minutes after morphine, or animals were allowed to undergo natural withdrawal from a single dose of morphine. Inhibition of ϵ but not γPKC prevented naloxone-precipitated allodynia 30 minutes after morphine administration in P7 rats. In contrast, both ϵ and γPKC inhibitors attenuated naloxone-precipitated allodynia in P21 rats. Allodynia was attenuated in P7 and P21 rats by administration of either ϵ or γPKC inhibitor when withdrawal was precipitated at 2 hours after morphine or animals underwent natural withdrawal. This work demonstrates that the role of ϵ and γPKC in acute withdrawal-induced allodynia is developmentally regulated in a temporally specific manner.

The intraspinal approach for controlling pain and spasticity is a safe alternative for patients who failed other less invasive modalities. It is rapidly gaining popularity as a valuable tool for this subset of patients. The safety and availability of implantable devices has helped expand the use of this route. The success of this alternative treatment is highly dependent on the physician’s skills and knowledge of the functional anatomy of the spinal cord, its coverings and its supporting structures.

Two basic approaches have been employed in experiments designed to test potential gene-based therapies for chronic pain in humans. First, local or spinal overexpression of neuropeptides, growth factors, and biosynthetic enzymes for neurotransmitters in non-neuronal cells has been tested in animals. Continued production and release of these antinociceptive proteins into the cerebrospinal fluid is analogous to intrathecal infusion of antinociceptive drugs. Second, overexpression of transgenes or knockdown of endogenous gene expression in primary or secondary neurons involved in nociception has been used in animal studies. Altered expression of neuropeptides, growth factors, enzymes, ion channels, or receptors in these nociceptive neurons can modulate pain transmission in an anatomically restricted, circuit-specific, and stimulation-dependent manner. Techniques employed in testing potential gene-based therapy for chronic pain include implantation of engineered cell lines, administration of antisense oligonucleotides or plasmids, and the use of viral vectors. Of the modalities tested to date, only intrathecal transplantation of engineered cells secreting antinociceptive gene products and delivery of therapeutic transgenes by herpes vectors demonstrate sufficient duration of expression to be useful for therapy of chronic pain.

Significant advances in the management of intractable pain and spasticity have occurred over the past two decades. This was largely a direct result of the discovery of spinal sites of action of the various analgesic and anti-spasticity agents and the clinical application of the intrathecal route for delivery of these centrally acting agents. Only two agents are FDA-approved for intrathecal use—namely morphine for intractable pain and baclofen for spasticity. However, a number of other intrathecal agents are used routinely in clinical practice, while other agents are considered experimental or unproven and are used sparingly or are regarded largely as being unsafe. The pharmacology of standard and investigational agents used intrathecally is reviewed in this article with particular attention to the mechanism of action, pharmacokinetics, indications for use, and evidence of clinical efficacy and safety profile.

Intrathecal drug-delivery systems have been used increasingly for management of pain and spasticity. The indications, efficacy, and cost-effectiveness of intrathecal therapy have not been established with certainty in randomized, controlled trials, but most available data indicate that intrathecal therapy can be a remarkably useful treatment of otherwise intractable pain and spasticity. Outcomes will undoubtedly improve further as we gain a better understanding of (and strict adherence to) patient selection criteria and mechanisms governing intrathecal drug actions while continuing to emphasize thoughtful patient and family education regarding therapeutic goals and their responsibility in helping to make the therapy successful.