Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy

Pain. 2014 Jul;155(7):1272-1279. doi: 10.1016/j.pain.2014.03.022. Epub 2014 Apr 2.


Central sensitization after peripheral nerve injury may result in ectopic neuronal activity in the spinal cord dorsal horn, implying a potential autonomous pain-generating mechanism. This study used peripheral nerve blockade and systemic lidocaine administration, with detailed somatosensory assessment, to determine the contribution of primary afferent input in maintaining peripheral neuropathic pain. Fourteen patients with neuropathic pain (7 with unilateral foot pain due to peripheral nerve injury and 7 with bilateral pain in the feet due to distal polyneuropathy) underwent comprehensive characterization of somatosensory function by quantitative sensory testing. Patients were then administered an ultrasound-guided peripheral nerve block with lidocaine and intravenous lidocaine infusion in randomized order. The effect of these interventions on spontaneous pain intensity and on evoked cold, warm, pinprick, and brush responses was assessed at each session. All patients had sensory disturbances at baseline. The peripheral nerve block resulted in a complete abolition of ipsilateral pain within 10 min (median) in all patients, with lidocaine plasma concentrations being too low to account for a systemic effect of the drug. Intravenous lidocaine infusion reduced the spontaneous pain by 45.5% (±31.7%), and it reduced mechanical and thermal hypersensitivity in most patients who displayed such signs. However, the improvement in evoked hypersensitivity was not related to the effect of the drug on spontaneous pain intensity. This study demonstrated that regardless of the individual somatosensory phenotype and signs of central sensitization, primary afferent input is critical for maintaining neuropathic pain in peripheral nerve injury and distal polyneuropathy.

Keywords: Any order; Word.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Afferent Pathways / physiopathology*
  • Aged
  • Aged, 80 and over
  • Anesthetics, Local / therapeutic use
  • Central Nervous System Sensitization / physiology*
  • Female
  • Humans
  • Hyperalgesia / physiopathology*
  • Infusions, Intravenous
  • Lidocaine / therapeutic use
  • Male
  • Middle Aged
  • Nerve Block / methods
  • Neuralgia / drug therapy
  • Neuralgia / physiopathology*
  • Pain Measurement
  • Peripheral Nerve Injuries / drug therapy
  • Peripheral Nerve Injuries / physiopathology*
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / physiopathology*
  • Polyneuropathies / drug therapy
  • Polyneuropathies / physiopathology*
  • Treatment Outcome
  • Young Adult


  • Anesthetics, Local
  • Lidocaine