The sodium-channel blocker lidocaine in subanesthetic concentrations reduces spontaneous and evoked pain in human painful neuroma

Nanna Brix Finnerup; Simon Haroutounian; Lone Nikolajsen

doi:10.1016/j.sjpain.2015.05.003

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The sodium-channel blocker lidocaine in subanesthetic concentrations reduces spontaneous and evoked pain in human painful neuroma

Nanna Brix Finnerup , Simon Haroutounian and Lone Nikolajsen

Published/Copyright: July 1, 2015

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From the journal Scandinavian Journal of Pain Volume 8 Issue 1

1 Neuropathic pain

Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. It commonly persists for years, may remain a lifelong problem, and is often associated with significant reduction in quality of life, decreased mood and sleep disturbance. Current available drug treatments often provide only partial pain relief and are only effective in a subgroup of patients [1]. It is therefore striking that Miclescu et al. in this issue of the Scandinavian Journal of Pain, demonstrated an almost complete pain relief from subanesthetic concentrations of lidocaine injected close to a neuroma in patients with peripheral nerve injury and neuroma pain [2].Thestudy wasadouble-blindrandomizedcross-over trial, in which lidocaine was given as 0.5% and 0.1% in randomized order. The lowest (0.1%) concentration of lidocaine was used as a control rather than saline in order to reduce the acute pain from the injection and it probable also helped preserve blinding. There was also a marked effect of the 0.1% low concentration lidocaine. This study is important for at least three reasons: (1) It can help us understand the mechanisms by which local anesthetics provide pain relief, (2) improve our understandingofmechanismsbywhich neuropathic pain is maintained, and (3) help to identify targets for pain treatment.

2 Local anesthetics and the mechanisms of neuropathic pain

Several editorial comments have reflected over the need for studies that can improve our understandingofhow local anesthetic blocks work [3,4]. Reports have suggested that anesthetic blocks as well as systemic administration of lidocaine may produce long-lasting effects outlasting the conduction blockade and that blocks distally to the site of the nerve lesion may produce complete pain relief [5,6], but the underlying mechanisms are unknown and properly controlled studies are lacking [4]. In the study by Miclescu et al. some patients had an effect that lasted more than 24h, but most patients had temporary, short-lasting effects [2]. The short-lasting effect found in most patients may not be as surprising as the long-lasting effects. However, the substantial analgesic effect of a sub-anesthetic dose of lidocaine on chronic neuroma pain is remarkable, and the study suggests that central sensitization and other central neuroplastic changes reported following nerve injury do not generate or maintain pain in the absence of ectopic dischargesfromafferentfibers. The authors found differences between the analgesic effect of local lidocaine on spontaneous pain and pain evoked from mechanical stimulationofthe neuroma, with the effect on spontaneous pain lasting longer [2]. This may reflect the lower intensity of spontaneous pain at baseline compared to pain evoked from local mechanical stimulationofthe neuroma, different thresholds for efficacy, or different underlying mechanisms/fibers involved. Similar differential effect, albeit different, was reported by Nyström and Hagbarth in 1981, where they showed that blocking a neuroma in two patients with phantom limb pain abolished tap-induced afferent discharges and the tap-induced accentuation of the phantom pain, while the spontaneous pain and spontaneous activity were unchanged [7]. We have previously found a lack of association between a reduction in spontaneous pain and dynamic mechanical and cold allodynia in patients with different types of peripheral neuropathic pain [8]. Further studies are warranted to get a better understanding of the mechanisms by which locally applied lidocaine reduce different pain characteristics.

3 Better treatments of neuropathic pain

How can we use the results from the paper by Miclescu et al. to improve the treatment of neuropathic pain? Only few patients reported prolonged relief, which suggest that injection of sub anesthetic doses of lidocaine is not a treatment that can be used to treat chronic pain patients. Many of the drugs we use today are unspe-cific centrally acting drugs which are associated with CNS-related and other dose-limiting side effects [1]. Peripherally-acting drugs have the advantage of fewer side effects and development of treatments targeting peripheral sites seems advantageous. The study by Miclescu et al. supports that further development of peripheral neuromodulation, topical agents, sodium channel blockers with preferential peripheral activity, and other locally acting treatments may lead to the development of treatments that are more effective and better tolerated than the currently available ones.

DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2015.04.026

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Conflict of interest: No conflict of interest declared.

References

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Published Online: 2015-07-01

Published in Print: 2015-07-01

Articles in the same Issue

https://doi.org/10.1016/j.sjpain.2015.05.003