Chronobiological characteristics of painful diabetic neuropathy and postherpetic neuralgia: Diurnal pain variation and effects of analgesic therapy

Clinical impressions suggest that neuropathic pain is often worse at night and significantly impairs sleep. However, the temporal pattern of neuropathic pain during waking hours has not been clearly characterized. Using clinical trial data, we have evaluated the diurnal variation of pain intensity before and during analgesic treatment in patients with diabetic neuropathy (DN) and postherpetic neuralgia (PHN). Pain intensity (0–10) measures throughout the day from a placebo-controlled trial of around-the-clock administration of gabapentin, morphine and a gabapentin–morphine combination in neuropathic pain patients were examined. Baseline data in untreated patients revealed no effect of day of week but a significant effect of time of day in both DN (P<0.001) and PHN (P<0.001) such that pain intensity progressively increases throughout the day. This temporal pattern is essentially preserved during treatment with gabapentin, morphine and their combination. Neuropathic pain intensity progressively increases throughout the day and this temporal profile appears to be unaffected by treatment with gabapentin and/or morphine. Advancing our understanding of the chronobiology of neuropathic pain may shed new light on various neurohormonal and neurophysiologic influences and lead to the identification of novel therapeutic targets. Furthermore, recognizing diurnal pain patterns may guide treatment strategies such as the targeted timing of analgesic therapies.