Pain quality predicts response to sodium channel blockade with lidocaine

Large trials of sodium channel blockers for neuropathic pain (NP) have been repeatedly disappointing despite compelling data implicating abnormal sodium channel function in NP. Pain qualities (e.g. burning, aching, sharp) may reflect underlying pain mechanisms. Therefore, the use of pain qualities to match individual patients to specific therapies has been anticipated, but thus far has never been demonstrated. We hypothesized that lidocaine induced analgesia in patients with NP would be predicted by differing pain qualities. Therefore, we prospectively collected baseline measurements of pain qualities with the Short Form McGill Pain Questionnaire (SF-MPQ) in 70 patients with NP. Patients then completed placebo-controlled targeted lidocaine infusions in a single-blind crossover design. Answers to several SF-MPQ sensory pain qualities (e.g. stabbing and sharp) were highly correlated, so we used exploratory factor analysis to uncover the number of independent underlying pain qualities these SF-MPQ items were actually measuring. Factor analysis identified two underlying independent qualities in our neuropathic pain patients: a stabbing-sharp quality and an independent aching-heavy quality. We used generalized estimating equations to examine whether these baseline qualities determined change in Visual Analog Scale of pain intensity (VAS) over time in response to lidocaine infusions. Patients with higher baseline levels of aching-heavy quality have markedly greater lidocaine induced reductions in VAS than those with low levels of aching-heavy quality (p=0.013). The interaction of pain quality with subsequent pain reduction was specific to aching-heavy quality, and not observed with stabbing-sharp quality or overall pain intensity. The interaction of aching-heavy quality with subsequent pain reduction was also specific to lidocaine infusions, and not observed with placebo infusions. Easily measured pain qualities may significantly predict subsequent change of pain VAS in response to sodium channel blockers, and rescue a place for sodium channel blockers in the armamentarium against neuropathic pain.