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. 2017 May 22;5(5):CD011669.
doi: 10.1002/14651858.CD011669.pub2.

Morphine for chronic neuropathic pain in adults

Tess E Cooper  1 , Junqiao Chen  2 , Philip J Wiffen  3 , Sheena Derry  3 , Daniel B Carr  4 , Dominic Aldington  5 , Peter Cole  6 , R Andrew Moore  3
Affiliations

Morphine for chronic neuropathic pain in adults

Tess E Cooper et al. Cochrane Database Syst Rev. .

Abstract

Background: Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the nervous system. Opioid drugs, including morphine, are commonly used to treat neuropathic pain. Most reviews have examined all opioids together. This review sought evidence specifically for morphine; other opioids are considered in separate reviews.

Objectives: To assess the analgesic efficacy and adverse events of morphine for chronic neuropathic pain in adults.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for randomised controlled trials from inception to February 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries.

Selection criteria: We included randomised, double-blind trials of two weeks' duration or longer, comparing morphine (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.

Data collection and analysis: Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables.

Main results: We identified five randomised, double-blind, cross-over studies with treatment periods of four to seven weeks, involving 236 participants in suitably characterised neuropathic pain; 152 (64%) participants completed all treatment periods. Oral morphine was titrated to maximum daily doses of 90 mg to 180 mg or the maximum tolerated dose, and then maintained for the remainder of the study. Participants had experienced moderate or severe neuropathic pain for at least three months. Included studies involved people with painful diabetic neuropathy, chemotherapy-induced peripheral neuropathy, postherpetic neuralgia criteria, phantom limb or postamputation pain, and lumbar radiculopathy. Exclusions were typically people with other significant comorbidity or pain from other causes.Overall, we judged the studies to be at low risk of bias, but there were concerns over small study size and the imputation method used for participants who withdrew from the studies, both of which could lead to overestimation of treatment benefits and underestimation of harm.There was insufficient or no evidence for the primary outcomes of interest for efficacy or harm. Four studies reported an approximation of moderate pain improvement (any pain-related outcome indicating some improvement) comparing morphine with placebo in different types of neuropathic pain. We pooled these data in an exploratory analysis. Moderate improvement was experienced by 63% (87/138) of participants with morphine and 36% (45/125) with placebo; the risk difference (RD) was 0.27 (95% confidence interval (CI) 0.16 to 0.38, fixed-effects analysis) and the NNT 3.7 (2.6 to 6.5). We assessed the quality of the evidence as very low because of the small number of events; available information did not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different was very high. A similar exploratory analysis for substantial pain relief on three studies (177 participants) showed no difference between morphine and placebo.All-cause withdrawals in four studies occurred in 16% (24/152) of participants with morphine and 12% (16/137) with placebo. The RD was 0.04 (-0.04 to 0.12, random-effects analysis). Adverse events were inconsistently reported, more common with morphine than with placebo, and typical of opioids. There were two serious adverse events, one with morphine, and one with a combination of morphine and nortriptyline. No deaths were reported. These outcomes were assessed as very low quality because of the limited number of participants and events.

Authors' conclusions: There was insufficient evidence to support or refute the suggestion that morphine has any efficacy in any neuropathic pain condition.

PubMed Disclaimer

Conflict of interest statement

TC: none known.

JC: none known.

PW: none known.

SD: none known.

DBC: none known; DBC is a specialised pain physician and has managed patients with chronic pain.

DA: is a specialist pain physician and manages patients with neuropathic pain. He has received lecture fees from Grünenthal (2014, 2015) and Pfizer (2016).

PC: none known; PC is a specialist pain physician and manages patients with neuropathic pain. PC received support from Boston Scientific (2014) for travel and accommodation at a scientific meeting; Boston Scientific does not market drugs.

RAM: has received grant support from Grünenthal relating to individual patient level analyses of trial data regarding tapentadol in osteoarthritis and back pain (2015). He has received honoraria for attending boards with Menarini concerning methods of analgesic trial design (2014), with Novartis (2014) about the design of network meta‐analyses, and RB on understanding pharmacokinetics of drug uptake (2015). He has received honoraria from Omega Pharma (2016) and Futura Pharma (2016) for providing advice on trial and data analysis methods.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Morphine versus placebo, outcome: 1.1 Moderate improvement.
1.1
1.1. Analysis
Comparison 1 Morphine versus placebo, Outcome 1 Moderate improvement.
1.2
1.2. Analysis
Comparison 1 Morphine versus placebo, Outcome 2 Substantial improvement.
1.3
1.3. Analysis
Comparison 1 Morphine versus placebo, Outcome 3 All‐cause withdrawal.
See this image and copyright information in PMC

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