Pain
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Enriched enrolment, randomised withdrawal (EERW) pain trials select, before randomisation, patients who respond by demonstrating a predetermined degree of pain relief and acceptance of adverse events. There is uncertainty over the value of this design. We report a systematic review of EERW trials in chronic noncancer pain together with a critical appraisal of methods and potential biases in the methods used and recommendations for the design and reporting of future EERW trials. ⋯ Shorter, small studies can be explanatory; longer, larger studies can inform practice. Current evidence is inadequate for valid comparisons in outcome between EERW and classical trials, although no gross differences were found. This systematic review provides a framework for assessing potential biases and the value of the EERW trials, and for the design of future studies by making recommendations for the conduct and reporting of EERW trials.
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Randomized Controlled Trial
Combination of morphine with nortriptyline for neuropathic pain.
First-line neuropathic pain drugs, including tricyclic antidepressants, are not always effective, and opioids have been recommended as second line. This trial evaluates a nortriptyline-morphine combination, compared with each monotherapy. In this randomized, double-blind crossover trial, patients with neuropathic pain were enrolled at 1 site between January 25, 2010, and May 22, 2014, and randomized in a 1:1:1 ratio using a balanced Latin square design to receive oral nortriptyline, morphine, and their combination. ⋯ Combination treatment resulted in moderate-severe constipation in 43% vs 46% with morphine (P = 0.82) and 5% with nortriptyline (P < 0.0001). Combination treatment resulted in moderate-severe dry mouth in 58% vs 49% with nortriptyline (P = 0.84) and 13% with morphine (P < 0.0001). This trial suggests superior efficacy of a nortriptyline-morphine combination over either monotherapy with constipation, dry mouth, and somnolence as the most frequent adverse effects.
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Choosing the most appropriate treatment for individual patients with low back pain (LBP) can be challenging, and clinical guidelines recommend taking into account patients' preferences. However, no tools exist to assess or compare patients' views about LBP treatments. We report the development and validation of the Low Back Pain Treatment Beliefs Questionnaire (LBP-TBQ) for use across different treatments in clinical practice and research. ⋯ Participants with stronger positive treatment beliefs were more likely to rank that treatment as their first choice, indicating good criterion validity (t values = 3.11-9.80, all P < 0.01, except pain medication effectiveness beliefs, t(339) = 1.35; P = 0.18). A short 4-item version also displayed good homogeneity (H = 0.43-0.66), internal consistency (α = 0.70-0.86), and stability (r = 0.82-0.85) and was significantly related to treatment choice (t values = 4.33-9.25, all P < 0.01). The LBP-TBQ can be used to assess treatment beliefs in primary care patients with LBP and to investigate the effects of treatment beliefs on treatment uptake and adherence.
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It is generally agreed that cold allodynia is a consequence of impaired (Aδ-fibre-mediated) central inhibition of C-nociceptive inputs. However, it is also known that C polymodal nociceptors are not activated at innocuous low temperatures. Recently, we demonstrated the contribution of C-tactile fibres to tactile allodynia. ⋯ Cold allodynia persisted after nerve compression and TRPV1 and TRPM8 desensitisation but was abolished by localised Cav3.2 blockade. In clinical subjects, C-fibre-mediated allodynia was observed without the need for experimental pain-producing manipulations. In conclusion, cold allodynia represents a non-TRPV1- and non-TRPM8-dependent phenomenon, which is mediated by low-threshold Cav3.2-expressing C fibres.