Differential effects of lidocaine on nerve growth factor (NGF)‐evoked heat‐ and mechanical hyperalgesia in humans
- 6 March 2012
- journal article
- Published by Wiley in European journal of pain
- Vol. 16 (4), 543-549
- https://doi.org/10.1016/j.ejpain.2011.08.004
Abstract
We investigated the effects of a non-specific sodium channel blocker (lidocaine) on heat pain thresholds and mechanical impact pain at day 7 and 21 after intradermal injection of 1 μg NGF. Measurements were performed in 12 healthy male subjects prior to and 5 min after intradermal injection of 150 μl lidocaine administered at concentrations of 0.01% (∼0.4 mM) and 0.1% (∼4 mM) to both NGF and control skin sites. NGF caused a maximum reduction of heat pain thresholds at day 7 (NGF 42.6 ± 0.6 vs. 49.4 ± 0.3 °C in control skin). Lidocaine sensitized normal skin for heat pain, but reduced heat hyperalgesia after NGF at day 7 (44.3 ± 0.8 °C, lidocaine 0.1%; p < 0.005). Pain upon supra-threshold mechanical impact stimulation was increased after NGF at day 7 (VAS 29 + 5) and massively enhanced at day 21 (VAS 64 + 5, p < 0.001). Lidocaine dose-dependently attenuated mechanically-induced pain at both control and NGF-treated sites. Maximum lidocaine effects on mechanical hyperalgesia were recorded at day 21 in NGF skin (pain reduction to VAS 37 ± 4, p < 0.00001). Repetitive impact stimuli caused increasingly more pain at the NGF sites at day 21 and this pain increase was efficiently suppressed by lidocaine 0.1%. Lidocaine differentially affects NGF-induced mechanical hyperalgesia (analgesic effect) and heat sensitivity of nociceptors (sensitizing effect). These opposing responses may be attributed to block of sodium channels vs. sensitization of TRPV1. NGF-evoked extreme mechanical impact pain indicates high action potential discharge frequencies, which might be more susceptible to lidocaine block.Keywords
This publication has 26 references indexed in Scilit:
- Nerve growth factor selectively decreases activity-dependent conduction slowing in mechano-insensitive C-nociceptorsPain, 2011
- NGF enhances electrically induced pain, but not axon reflex sweatingPain, 2011
- Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig corneaThe Journal of Physiology, 2009
- Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meningesThe Journal of Physiology, 2008
- Unraveling the Story of NGF-mediated Sensitization of Nociceptive Sensory Neurons: ON or OFF the Trks?Molecular Interventions, 2007
- Use-Dependent Block by Lidocaine but Not Amitriptyline Is More Pronounced in Tetrodotoxin (TTX)-Resistant Nav1.8 Than in TTX-Sensitive Na+ ChannelsJournal of Pharmacology and Experimental Therapeutics, 2006
- Novel class of pain drugs based on antagonism of NGFTrends in Pharmacological Sciences, 2006
- Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaineBritish Journal of Pharmacology, 2004
- Intradermal recombinant human nerve growth factor induces pressure allodynia and lowered heat-pain threshold in humansNeurology, 1997
- A novel technique for the evaluation of mechanical pain and hyperalgesiaPain, 1991