Analgesic effect of dextromethorphan in neuropathic pain

BACKGROUND: Dextromethorphan, a clinically available N-methyl-D-aspartic acid (NMDA) receptor antagonist, has an analgesic effect in patients with diabetic neuropathy. The aim of this study was to evaluate the analgesic and adverse effects of a single high dose of dextromethorphan on spontaneous pain in patients suffering long-term neuropathic pain of traumatic origin. METHODS: Fifteen patients with post-traumatic neuropathic pain participated in this placebo-controlled, double-blind, randomized crossover study. On two separate occasions, the participants received 270 mg of dextromethorphan hydrobromide or placebo. Pain intensity, adverse effects and serum concentrations of dextromethorphan and metabolites were registered. RESULTS: Dextromethorphan had a statistically significant analgesic effect compared with placebo, but the effect varied markedly among the patients. Light-headedness was the most important adverse effect reported. Extensive metabolizers of dextromethorphan had an apparently better analgesic effect than poor metabolizers. CONCLUSION: This report indicates that a single high dose of dextromethorphan has an analgesic effect in patients with neuropathic pain of traumatic origin. The main metabolite dextrorphan seems to be important for the analgesic effect. At the relatively high dose studied, the clinical usefulness of dextromethorphan is limited to that portion of the patient population experiencing analgesia without an unacceptable level of adverse effects.     

A qualitative systematic review of peri-operative dextromethorphan in post-operative pain

BACKGROUND: The N-methyl-D-aspartate (NMDA) receptor antagonist, dextromethorphan (DM), has received interest as an adjunctive agent in post-operative pain management. Clinical trials have been contradictory. This systematic review aims to evaluate the available literature examining the analgesic efficacy of DM in post-operative patients. METHODS: Twenty-eight randomized, double-blind, clinical studies, with 40 comparisons, including a variety of dosing regimens comparing DM treatment with placebo, were included. Meta-analysis was intended but deemed to be inappropriate because of the substantial difference in methodology and reporting between trials. The outcome measures (pain scores at rest, time to first analgesic request and supplemental analgesic consumption) were evaluated qualitatively by significant difference (P<0.05) as reported in the original investigations. RESULTS: DM did not reduce the post-operative pain score with a clinically significant magnitude. The time to first analgesic request was significantly prolonged in most comparisons with DM. Significant decreases in supplemental opioid consumption were observed in the majority of parenteral DM studies and in about one-half of the oral studies. The decreases were of questionable clinical importance in most comparisons, although a relationship between a decrease in opioid consumption and opioid-related side-effects was established in some studies. CONCLUSION: Based on the studies available, DM has the potential to be a safe adjunctive agent to opioid analgesia in post-operative pain management, but the consistency of the potential opioid-sparing and pain-reducing effect must be questioned. Consequently, it is not possible to recommend dose regimens or routine clinical use of DM in post-operative pain. The route of administration may be important for the beneficial effect.     

Perioperative dextromethorphan reduces postoperative pain after hysterectomy.

We studied the effect of dextromethorphan, an N-methyl-D-aspartate antagonist, on analgesic consumption and pain scoring after abdominal hysterectomy. In this double-blinded study, 50 patients were randomized into two groups. Group DM was given oral dextromethorphan 40 mg with their premedication, then 40 mg three times per day for the next 2 days. Group P received placebo at identical times. Postoperative analgesic requirements were assessed using a patient-controlled analgesia system and subsequent oral analgesic intake using a set protocol. Pain was assessed at rest and on movement using a visual analog scale 4, 24, 48, and 72 h after the operation. Median pain scores at rest were significantly lower at 48 and 72 h and also for the sum of all resting pain scores. Mean morphine consumption was less in Group DM (1.1 vs 1.5 mg/h; P = 0.054). Usage of oral diclofenac, given every 8 h as needed, did not differ between groups, but consumption of codydramol (paracetamol 500 mg and dihydrocodeine 10 mg) was significantly less in Group DM. We conclude that the use of oral dextromethorphan has an analgesia-sparing effect and some beneficial effects on pain scoring at rest after abdominal hysterectomy. Implications: Patients given dextromethorphan before and after surgery had a significant reduction in some pain scores at rest, but not on movement. There was a trend to lower morphine requirements in the first 24 h. Over the next 48 h, oral analgesic usage was significantly reduced.     

The N-methyl-D-aspartate-receptor antagonist dextromethorphan lacks analgesic effect in a human experimental ischemic pain model

BACKGROUND: N-methyl-D-aspartate-receptor antagonists may be useful in pain management. The aim of this study was to evaluate dextromethorphan (DEX), a commonly used oral antitussive drug with NMDA-receptor antagonistic properties, in respect of its analgesic properties as single drug and co-administered with morphine (MO) on experimental ischemic pain. In addition, the analgesic effects of another clinically available NMDA-receptor antagonist, ketamine (KET) as well as of morphine (MO) were tested as active controls. METHODS: Nineteen healthy volunteers were included in the study. Experimental ischemic pain was induced using the forearm tourniquet test. Placebo (PLAC), oral DEX (30 and 90 mg, respectively), KET (9 microg kg(-1) min(-1) i.v.), MO (0.1 mg kg(-1), i.v.) and the DEX+MO and KET+MO combinations were evaluated during eight separate experiments. Development of ischemic pain was rated by visual analog scale (VAS) every minute over 30 min and ratings were summed as sum of pain scores (SPS). RESULTS: DEX by itself did not influence SPS compared to PLAC. The DEX+MO co-administration did not enhance MO-induced analgesia. MO and KET reduced pain ratings by 27% and 39%, respectively. The KET+MO combination showed no enhancement of the analgesic effect in comparison with the respective drugs in monotherapy. CONCLUSION: DEX in clinical doses has no effect on the present acute ischemic pain model and does not influence MO-induced analgesia. Further studies on other pain modalities are needed in order to evaluate the potential use of DEX in pain treatment.     

微小RNA在病理性疼痛中的作用

背景 微小RNA(microRNAs,miRNAs)是目前研究最为广泛的一类内源性非编码小分子RNA,长度范围在16～29个核苷酸之间,通过转录后调节机制调节基因的表达.最近研究发现miRNAs在不同的病理性疼痛模型中均有不同程度的表达,可能参与慢性疼痛以及急性伤害性刺激伤害感受过程的基因调节机制,调控几种与疼痛相关转录物的表达. 目的 对miRNAs在病理性疼痛中作用的研究有助于我们更清楚地了解病理性疼痛的产生和维持分子学机制,为疼痛治疗提供了新的方向. 内容 主要介绍miRNAs在炎症性痛、神经病理性痛以及疼痛相关性疾病中的表达情况,以及miRNAs在慢性病理性疼痛中的可能作用. 趋势 鉴于miRNAs在病理性疼痛的产生中具有重要作用,miRNAs将有可能作为治疗疼痛性疾病的一种新型的研究工具、生物标记和潜在的药物治疗靶点.     

巨噬细胞在神经病理性疼痛中的作用

神经病理性疼痛（neuropathic pain, NP）是指由躯体感觉系统的损害或疾病导致的疼痛。NP的发病机制复杂,与免疫调节有关。巨噬细胞是体内重要的免疫细胞,在体内通过自身极化和神经免疫相互作用参与神经损伤后的外周及中枢敏化形成过程,促进NP的发展。文章对巨噬细胞在NP中的作用进行综述,研究巨噬细胞在NP形成与...     

The intravenous ketamine test: a predictive response tool for oral dextromethorphan treatment in neuropathic pain

IV infusion tests performed to predict subsequent response to oral analgesics are an increasingly popular method used to enhance medical care and conserve resources. Because no infusion test is completely accurate, the potential benefits of these tests must be weighed against the frustration and waste in resources encountered with false-positive results, and the failure to use a potentially beneficial treatment with false-negative results. In recent years, drugs that act antagonistically at N-methyl-d-aspartate receptors have been shown to be valuable adjuncts in the treatment of pain. To determine the predictive value of small-dose (0.1 mg/kg) IV ketamine on an oral dextromethorphan (DX) treatment regimen, we analyzed the analgesic response to these drugs in 25 patients at 2 tertiary care military treatment facilities, institutions at which DX is not readily accessible. When >/=50% response for both drugs was used as the outcome measure for success, the positive predictive value of the ketamine test was 64%, the negative predictive value 73%, and the observed agreement 68%. However, when >/=67% relief with ketamine was used as an outcome measure (as determined by a receiver operating characteristic curve), the positive predictive value was 90%, the negative predictive value 80%, and the observed agreement increased to 84%. Based on these results, we conclude that an IV ketamine test may be useful in predicting response to oral DX. More research is needed to determine the ideal candidates for such a test, and the optimal dose and cutoff value for the response to ketamine.     

The pain control infusion pump for postoperative pain control in shoulder surgery.

PURPOSE: This study was initiated to evaluate the effect of a pain control infusion catheter in managing postoperative pain. Type of Study: In a prospective, randomized trial, 62 consecutive patients undergoing arthroscopic subacromial decompression had an indwelling pain control infusion catheter placed at the operative site. Materials and Methods: Thirty-one patients received 0.25% bupivacaine and 31 patients received saline infusions, each at a constant rate of 2 mL per hour. Patients evaluated their pain by visual analog scale, and also tabulated the amount of narcotic and nonnarcotic medication used each day in the first week of surgery. RESULTS: There was a statistically significant difference in pain in all parameters tested in the bupivacaine group as compared with the saline control group (P <.05). CONCLUSIONS: The bupivacaine pain control infusion pump is an effective means of decreasing postoperative pain.     

The role of psychological factors in chronic pain

The traditional view conceptualizes pain as being directly associated with the extent of physical pathology. The observations that there are a number of patients who report pain in the absence of physical pathology, the converse, asymptomatic individuals who evidence objective physical pathology, the inconsistency in response of patients with identical diagnoses, and the low association between impairments and disability suggest that factors other than physical pathology contribute to the reports of pain. The role of behavioral, cognitive, and affective factors have each been shown to have direct effects on the report of pain, adaptation, and response to treatment, as well as indirect effects by influencing sympathetic nervous system and neurochemical factors associated with nociception. The direct and indirect effects of behavioral (operant), cognitive, and affective factors in chronic pain are described.     

神经病理性疼痛的表观遗传学发展方向

背景 神经病理性疼痛(neuropathic pain,NP)是由神经系统的损害或炎症引起的一种常见而特殊的慢性疼痛,以痛觉过敏、异常痛敏和自发痛为特征.目前发病机制不清,发病率逐年上升,处理非常棘手而且目前的治疗方法疗效不佳,是医学领域的挑战性研究课题. 目的 综述表观遗传学在疼痛中的研究状况. 内容 主要对表观遗传学的基本原理、生物学作用以及表观遗传学在疼痛中的研究进展进行综述. 趋向 表观遗传学在NP中的作用将为人们进一步深入阐明疼痛机制提供新的思路,为NP的治疗提供新的策略.     

The role of articular cartilage in patellofemoral pain

This article describes a conservative program of treatment for patellofemoral pain of chondromalacic origin. It has become obvious that patellofemoral pain syndromes are derived from cartilage degradation and from soft-tissue changes, including tendinitis and neuromatous degeneration.     

Preincisional dextromethorphan decreases postoperative pain and opioid requirement after modified radical mastectomy

PURPOSE: To examine whether preincisional dextromethorphan (DM) improved analgesia after modified radical mastectomy (MRM). METHODS: Sixty patients (ASA I-II) scheduled for MRM were included and randomly allocated into two groups. Patients in the treatment group (DM) received 40 mg DM and 20 mg chlorpheniramine maleate (CPM) i.m., and those in the control group received 20 mg CPM i.m. alone 30 min before skin incision. Meperidine, 1 mg x kg(-1) i.m., was given for postoperative pain relief as required. The time to first meperidine injection, total meperidine consumption, worst pain score, bed-rest time, and side effects were recorded every 24 hr for 48 hr after surgery by a resident anesthesiologist on a double-blind basis. RESULTS: A longer time to first meperidine injection (19.2 +/- 1.6 vs 1.5 +/- 0.23 hr, P < 0.001) and lower meperidine consumption (0[10] vs 75[50] mg, median [interquartile range], P < 0.001) were observed in the DM group than in the control group. The bed-rest time was shorter in the DM than in the control group (18.0[4] vs 23.0[19] hr, P < 0.001). No difference was noted in worst VAS pain score. Meperidine-related side effects (nausea, vomiting, pruritus, dizziness, headache) were more frequent in the control (10/30) than in the DM group (3/30, P < 0.05). The number of patients who required meperidine injection for pain relief was lower in the DM (7/30) than in the control group (25/30, P < 0.005). No DM- or CPM-associated side effects were observed. CONCLUSION: Preincisional IM. DM treatment decreased postoperative pain and opioid requirement after MRM surgery.     

Preoperative oral dextromethorphan does not reduce pain or analgesic consumption in children after adenotonsillectomy

In this randomized, double-blinded, placebo-controlled, prospective study, we evaluated the analgesic efficacy of dextromethorphan 0.5 mg/kg or 1.0 mg/kg p.o. 1 h before adenotonsillectomy in 57 children 6-12 yr of age. Anesthetic management was standardized. Morphine 0.075 mg/kg i.v. and acetaminophen 25-35 mg/kg p.r. were administered after anesthetic induction but before the start of surgery. A 4-point behavioral score (1 = asleep, 2 = awake and calm, 3 = awake and crying, 4 = thrashing) was recorded on admission to and discharge from the postanesthesia care unit (PACU). In the PACU, pain was assessed with Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and recorded every 15 min until the patient was transferred to the day surgery unit (DSU). In the DSU, patients rated their pain using a 10-cm baseline 0-10 visual analog pain scale (VAS) every 30 min until they were discharged home. A 24-h VAS was obtained by phone interview, and parental satisfaction was scored (yes/no) regarding their child's postoperative analgesia. Morphine 0.025 mg/kg i.v. was administered to children with CHEOPS score >6, who verbalized pain, or who were crying in any consecutive 5-min observation periods in the PACU. Total morphine consumption was recorded. The study groups were comparable with respect to demographic variables. We were unable to detect any differences between study groups with respect to postoperative morphine consumption, CHEOPS, behavior scores, VAS, or parental satisfaction. Implications: Premedication with dextromethorphan 0.5 or 1.0 mg/kg p.o. does not improve postoperative analgesia in school-aged children who receive preemptive morphine 0.075 mg/kg i.v. and acetaminophen 25-35 mg/kg p.r. during nitrous oxide and desflurane anesthesia for adenotonsillectomy.     

The effect of dextromethorphan, alone or in combination with ibuprofen, on postoperative pain after minor gynaecological surgery

BACKGROUND: Experimental studies have demonstrated that peripheral tissue injury may lead to hyperexcitability of nociceptive neurones in the dorsal horn, in part mediated by N-methyl-D-aspartate (NMDA)-receptor mechanisms. Sensitisation of dorsal horn neurones may be an important contributor to postoperative pain. The aim of the present study was to investigate the effect of the NMDA-receptor antagonist dextromethorphan on pain after minor gynaecological surgery, and to evaluate a potential additive effect with ibuprofen. METHODS: In a double-blind, placebo-controlled study, 100 patients scheduled for elective termination of pregnancy were randomised to receive placebo, oral ibuprofen 400 mg, oral dextromethorphan 120 mg, or a combination of ibuprofen 400 mg and dextromethorphan 120 mg, 1 h before surgery. Pain and analgesic requirements were assessed 0.5, 1 and 2 h after operation. RESULTS: We observed no effect of dextromethorphan on visual analogue scale (VAS) pain scores or analgesic consumption, and no additive or synergistic analgesic effects between ibuprofen and dextromethorphan. Ibuprofen reduced pain scores compared with placebo, and analgesic consumption compared with both placebo and dextromethorphan. The combination of ibuprofen and dextromethorphan increased preoperative nausea compared with both placebo and ibuprofen, whereas no statistically significant side effects were observed with dextromethorphan alone. CONCLUSION: No analgesic effects of oral dextromethorphan 120 mg on pain after surgical termination of labour, and no additive analgesic effects when combined with ibuprofen 400 mg, were observed. Ibuprofen reduced both VAS pain scores and analgesic consumption compared with placebo.     

The nurse's role in the postoperative pain management

Ward nurses have a central role in postoperative pain management. Pain medication is prescribed by anesthetists and surgeons, but it is ward nurses who spend more time with patients and have the responsibility for assessing patient's pain intensity, administering some prescribed analgesic treatments and monitoring their efficacy. Regular monitoring of patients' pain intensity by ward nurses is important in assessing the standard of care provided and in early detection of treatment side effects. New analgesic techniques such as epidural analgesia require extensive, systematic monitoring by nursing staff. There is increasing interest in establishing close cooperation and partecipation of ward nurses in day- to- day management of pain. In conclusion the quality of care provided by ward nurses is an important factor for the quality of patients' postoperative care, and nursing staff should be given the support they need to effectively treat pain.