Differential analgesic effects of subanesthetic concentrations of lidocaine on spontaneous and evoked pain in human painful neuroma: A randomized, double blind study

Abstract

Background Both peripheral nerve injury and neuroma pain are the result of changes in sodium channel expression. Lidocaine selectively inhibits the spontaneous ectopic activity by binding to sodium channels. Subanesthetics concentrations of lidocaine are able to produce a differential block of the ectopic discharges, but not propagation of impulses, suppressing differentially the associated neuropathic pain symptoms. The aim of this study was to investigate the differences between the analgesic effects of lidocaine 0.5% and a control group of lidocaine 0.1% on several neuroma related pain modalities. Methods Sixteen patients with neuropathic pain due to painful neuromas caused by nerve injury participated in this randomized, double-blind experiment. The patterns of sensory changes were compared before and after injection of 1ml lidocaine 0.5% and 0.1% close to the neuroma, the sessions being 1-2 weeks apart. Spontaneous and evoked pains were assessed using a visual analogue scale (VAS), quantitative and qualitative sensory testing. The primary end-point measure was defined as the change in pain score measured from baseline until 60min after injection. Assessments of spontaneous pain and evoked pain were done post injection at 15s, 30s, 1min, and at 5-min intervals for the first 30-min post injection and then every 10-min to 1 hr post injection. The assessments of pain were performed between the limbs in the following order: spontaneous pain, then assessment of dynamic mechanical allodynia and then hyperalgesia. Results Lidocaine dose-dependently reduced spontaneous and evoked pain scores by more than 80% with maximum effects between 1 and 5min for evoked pain and between 3 and 15min for spontaneous pain. While evoked pain normalized rapidly reaching about 50% of the control level 20min after the injection, spontaneous pain levels continue to be lower in comparison with baseline values for more than 60min. When comparing the time course of analgesia between spontaneous and evoked pain, lidocaine-induced a greater reduction of evoked pain, but with shorter duration than spontaneous pain. The differences between evoked pain and spontaneous pain were statistically significant in both groups (lidocaine 0.5% group; p = 0.02 and lidocaine 0.1% group; p = 0.01). Reproducibility was high for all assessed variables. Surprisingly, both lidocaine concentrations produced a sensory loss within the area with hyperalgesia and allodynia: hypoesthesia occurred earlier and lasted longer with lidocaine 0.5% (between 30s and 5min) in comparison with lidocaine 0.1% (p = 0.018). Conclusion Differential analgesic effects of subanesthetic concentrations of local lidocaineon evoked and spontaneous pain in human neuroma suggest that different mechanisms underlie these two key clinical symptoms. Spontaneous pain and evoked pain need an ongoing peripheral drive and any possible CNS amplification change is temporally closely related to this peripheral input. Implications Painful neuroma represents a clinical model of peripheral neuropathic pa...

Neuropathic Pain: Central vs. Peripheral Mechanisms

“…For example, dorsal horn neurons exhibit elevated expression of the chemokine SDF-1α/CXCL12 in a CIPN model [76][77][78], CXCL13 in a rat SNL model [79], and CCL3 and its receptor CCR5 in CCI in rats [80•, 81, 82]. Proinflammatory cytokines such as interferon-γ activate spinal microglia, a process that underlies many of the neuropathy-induced changes in spinal neuron behavior, Lidocaine injection close to the injury of post-surgical neuroma patients [50] Dose-dependent reduction in spontaneous and evoked pain scores by more than 80% Persistent post-herniorrhaphy pain Bupivacaine infiltration of tender points, ultrasound-guided, placebo-controlled Significantly greater analgesia and reduced evoked pain response when compared with placebo Persistent pain after breast cancer surgery (PPBCS) (pilot study)…”

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

“…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 discharges from afferent fibers. The authors found differences between the analgesic effect of local lidocaine on spontaneous pain and pain evoked from mechanical stimulation of the 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 stimulation of the neuroma, different thresholds for efficacy, or different underlying mechanisms/fibers involved.…”

“…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]. The study was a double-blind randomized cross-over trial, in which lidocaine was given as 0.5% and 0.1% in randomized order.…”

“…Reports have suggested that anesthetic blocks as well as systemic administration of lidocaine may produce longlasting effects outlasting the conduction blockade and that blocks distally to the site of the nerve lesion may produce complete pain DOI 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 24 h, but most patients had temporary, short-lasting effects [2]. The shortlasting effect found in most patients may not be as surprising as the long-lasting effects.…”

Treatment of Radiation-Induced Oral Mucositis Using a Novel Accepted Taste of Prolonged Release Mucoadhesive Bi-medicated Double-Layer Buccal Films

“…The high analgesic effect was due to the dual analgesic effect of DK and LC. It may be due to the combination of the analgesic effect of lidocaine through the accumulation of Na + channels on the site of damage whereas the central analgesic action was through inhibition of central pain receptors by DK and LC (64,65). The later explains why the patient will feel less pain rapidly and will have a strong analgesic and extended anti-inflammatory effect for a longer period when compared to the commercial products.…”