The journal of pain : official journal of the American Pain Society
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The purpose of the study was to examine the effect of 3 different application strategies for transcutaneous electrical nerve stimulation (TENS) on neuropathy-induced allodynia and dorsal horn neurotransmitter content. Rats were treated with high-frequency, low-frequency, or a combination of high and low-frequency stimulation. TENS was delivered through self-adhesive electrodes daily for 1 hour to rats with a right-sided chronic constriction injury (CCI). Stimulation was delivered to skin or acupuncture points on the left and mechanical and thermal pain thresholds were assessed in the right hind paw. Neurotransmitter content was assessed bilaterally in the dorsal horn of the spinal cord. Daily, high-frequency or a combination of high- and low-frequency TENS reduced mechanical (P < .001), but not thermal allodynia in the right hind paw when compared with untreated CCI rats. Daily high frequency TENS elevated the dorsal horn synaptosomal content of GABA bilaterally (P < .014) and a combination of high- and low-frequency TENS elevated the dorsal horn content of aspartate (P < .001), glutamate (P < .001) and glycine (P < .001) bilaterally over that seen in untreated CCI rats. The present findings support a contralateral approach to the application of TENS and suggest that distinct strategies for TENS application may differentially alter neurotransmission in the central nervous system. ⋯ Because CCI rats are reminiscent of humans with neuropathy, daily high or a combination of high- and low-frequency TENS may reduce mechanical allodynia in humans with neuropathic pain. Because the 2 intervention strategies produce distinctive alterations in spinal cord neurotransmitter content, each may represent a distinctive option for treatment.
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Chronic noncancer pain is common and use of opioids is increasing. Previously published guidelines on use of opioids for chronic noncancer pain have been based primarily on expert consensus due to lack of strong evidence. We conducted searches on Ovid MEDLINE and the Cochrane databases through July 2008 to identify studies that addressed one or more of 37 Key Questions that a multidisciplinary expert panel identified as important to be answered to generate evidence-based recommendations on the use of opioids for chronic noncancer pain. A total of 14 systematic reviews, 38 randomized trials not included in a previously published systematic review, and 13 other studies met inclusion criteria. Almost all of the randomized trials of opioids for chronic noncancer pain were short-term efficacy studies. Critical research gaps on use of opioids for chronic noncancer pain include: lack of effectiveness studies on long-term benefits and harms of opioids (including drug abuse, addiction, and diversion); insufficient evidence to draw strong conclusions about optimal approaches to risk stratification, monitoring, or initiation and titration of opioid therapy; and lack of evidence on the utility of informed consent and opioid management plans, the utility of opioid rotation, the benefits and harms specific to methadone or higher doses of opioids, and treatment of patients with chronic noncancer pain at higher risk for drug abuse or misuse. ⋯ Currently, clinical decisions regarding the use of opioids for chronic noncancer pain need to be made based on weak evidence. Research funding priorities need to be set to address these critical research needs if the care of patients with chronic noncancer pain is to improve.
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Practice Guideline
Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.
Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related policies. ⋯ Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.
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Intraplantar injection of bee venom (BV) produces persistent spontaneous nociception (PSN) and hyperalgesia, as well as obvious inflammatory swelling, in the paws of injected rats. The present study was designed to determine the peripheral roles of mitogen-activated protein kinase (MAPK) signal transduction pathways in BV-induced nociception and inflammation. We examined the effect of intraplantar injection of an ERK1/2 inhibitor, PD98059, and a p38 inhibitor, SB202190, on BV-induced PSN, mechanical hyperalgesia, and inflammatory swelling. We found that (1) pretreatment with SB202190 (0.1 to 10 microg) had no effect on BV-induced PSN, whereas pretreatment with PD98059 (0.1 to 100 microg) produced a significant and dose-dependent inhibition of BV-induced PSN; (2) pretreatment with PD98059 (0.1 to 100 microg) had no effect on BV-induced decreases in paw withdrawal mechanical threshold (PWMT), while pretreatment with SB202190 (0.1 to 10 microg) produced an obvious prevention of the BV-induced decrease in PWMT; and (3) pretreatment with PD98059 (0.1 to 100 microg) had no effect on BV-induced increase in paw volume (PV), whereas pretreatment with SB202190 (0.1 to 10 microg) produced a dose-related inhibition of BV-induced increases in PV. No contralateral drug treatments, even at the highest dose, had any effect on BV-induced PSN, PWMT or PV, ruling out the systemic effect of these drugs. These results suggest that peripheral MAPK signal transduction pathways may play differential roles in bee venom-induced nociception and inflammation. Targeting specific peripheral MAPKs might prove effective in the treatment of persistent pain and inflammation. ⋯ The present article showed that intraplantar injection of different MAPK inhibitors produced differential effects on bee venom-induced nociception and inflammation, suggesting that the peripheral MAPK signal transduction pathways have differential roles. Targeting specific peripheral MAPKs might prove effective in the treatment of persistent pain and inflammation.
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Iatrogenic errors producing serious and often preventable injury occur frequently in hospitalized patients, particularly in children. Little is known about the epidemiology of analgesic medication errors in patients being discharged from the hospital. The goal of this study was to describe the epidemiology of controlled substance prescription errors by physicians-in-training for children being discharged from the hospital. We conducted a prospective, observational study of the analgesic prescriptions and discharge forms of 241 pediatric patients discharged from a Children's Center of a major urban teaching hospital from November 2003 to April 2004. All patients who were actively followed by the Pediatric Pain Service at the time of their discharge and were discharged with an analgesic prescription were included in the study. Primary outcome variables were the percentage of prescriptions that contained at least 1 medication error or potential adverse drug event. Errors were defined using the Institute for Safe Medication Practices' (ISMP) List of Error-Prone Abbreviations, Symbols, and Dose Designations, literature review, expert panel consensus, and the Johns Hopkins Department of Pharmacy hospital formulary. Two hundred forty-one patients who received 314 prescriptions were included in this study. Prescription errors were common; 257 of 314 (82%) of the prescriptions examined contained 1 or more errors. The most common errors were missing or wrong patient weight (n = 127, 77%), incomplete dispensing information (n = 167, 53%), and no or wrong date on prescription (n = 19, 6%). Nine prescriptions (2.9%) had the potential for significant medical injury and were considered potential adverse drug events. Discharge prescription errors for children requiring potent, opioid analgesic drugs in the management of pain are common, and nearly 3% could cause significant harm. The high rate of prescribing errors highlights the importance of developing, testing and implementing effective error-prevention strategies, especially in high-risk medications such as narcotics. ⋯ Narcotic prescriptions written by trainees at discharge from a pediatric hospital are error prone and nearly 3% have the potential to cause significant harm. With a low therapeutic profile, the hospital may consider a review/verification process to reduce the risk of patient harm.