There is tremendous inter-patient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for “precision medicine”, or personalized pain therapeutics (i.e., empirically-based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain, and the success rates for putative analgesic drugs in Phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.

Objective: To assess the efficacy and tolerability of pregabalin for the treatment of central neuropathic pain after spinal cord injury (SCI).Methods: Patients with chronic, below-level, neuropathic pain due to SCI were randomized to receive 150 to 600 mg/d pregabalin (n 5 108) or matching placebo (n 5 112) for 17 weeks. Pain was classified in relation to the neurologic level of injury, defined as the most caudal spinal cord segment with normal sensory and motor function, as above, at, or below level. The primary outcome measure was duration-adjusted average change in pain. Key secondary outcome measures included the change in mean pain score from baseline to end point, the percentage of patients with $30% reduction in mean pain score at end point, Patient Global Impression of Change scores at end point, and the change in mean pain-related sleep interference score from baseline to end point. Additional outcome measures included the Medical Outcomes Study-Sleep Scale and the Hospital Anxiety and Depression Scale.Results: Pregabalin treatment resulted in statistically significant improvements over placebo for all primary and key secondary outcome measures. Significant pain improvement was evident as early as week 1 and was sustained throughout the treatment period. Adverse events were consistent with the known safety profile of pregabalin and were mostly mild to moderate in severity. Somnolence and dizziness were most frequently reported.Conclusions: This study demonstrates that pregabalin is effective and well tolerated in patients with neuropathic pain due to SCI. Chronic pain is present in approximately two-thirds of patients after spinal cord injury (SCI), with nearly one-third rating their pain as severe. 1 Chronic central neuropathic pain, which results from damage to the central sensory system itself, 2 occurs in approximately 40% of patients with SCI. 3 This pain is often severe and refractory to treatment, which includes anticonvulsants, antidepressants, analgesics, and antispasticity medications. [4][5][6][7] As a result, central neuropathic pain after SCI has a substantial impact on patient function, sleep, and overall quality of life. [8][9][10] Pregabalin (Lyrica; Pfizer Inc., New York, NY), an a 2 d ligand, is approved for the treatment of neuropathic pain in more than 100 countries, 11 including the treatment of central and peripheral neuropathic pain in the European Union, 12 peripheral neuropathic pain in Japan, 11 and peripheral neuropathic pain due to diabetic peripheral neuropathy or postherpetic neuralgia in the United Classification of evidence: