The effect of a monoclonal antibody to calcitonin-gene related peptide (CGRP) on injury-induced ectopic discharge following lingual nerve injury

NEUROSCIENCE LETTERS

卷:505

Article

Bowler, Katie E.¹  Worsley, Matthew A.¹  Broad, Lisa²  Sher, Emmanuel²  Benschop, Robert³  Johnson, Kirk³  Boissonade, Fiona M.¹  Robinson, Peter P.¹  Yates, Julian M.¹ 

[1] Univ Sheffield, Sch Clin Dent, Unit Oral & Maxillofacial Med & Surg, Sheffield S10 2TA, S Yorkshire, England

[2] Eli Lilly, Erl Wood Manor, Windlesham GU20 6PH, Surrey, England

[3] Eli Lilly, Indianapolis, IN 46225 USA

关键词: Lingual nerve injury;    Ectopic activity;    Calcitonin gene-related peptide;    Immunoneutralisation;    Monoclonal antibody;    Neuropathic pain;   

DOI  :  10.1016/j.neulet.2011.09.072

来源: Elsevier

【 摘 要 】

The development of ectopic neural discharge at a site of peripheral nerve injury is thought to contribute to the initiation of sensory disturbances and pain. We have previously shown that this discharge can be initiated or increased by the neuropeptide calcitonin gene-related peptide (CGRP). We have now studied a potential therapeutic approach to reducing the discharge by evaluating the effect of a systemically administered monoclonal antibody to CGRP on injury-induced activity in the lingual nerve. In 16 anaesthetised adult ferrets the left lingual nerve was sectioned. One day after the injury, the animals received a subcutaneous injection of either a monoclonal antibody to CGRP or a vehicle control. Three days after the injury, under a second anaesthetic, single-unit electrophysiological recordings were made from central to the injury site (469 and 391 units were analysed in antibody and vehicle groups, respectively), and the proportion of units that were spontaneously active was determined. In the vehicle-treated animals 6.4 +/- 2.7 [SEM]% of the units were spontaneously active, with conduction velocities of 8.8-40.8 m/s and discharge frequencies of 0.03-2.7 Hz. In the monoclonal antibody-treated animals 5.7 +/- 2.0% of the units were spontaneously active, with conduction velocities of 13.9-38.8 m/s and discharge frequencies of 0.07-1.8 Hz. There was no significant difference between these two groups (for spontaneous activity and conduction velocity: p > 0.05, Student's t-test; for discharge frequency: p > 0.05. Mann-Whitney test), suggesting that the spontaneous activity initiated by a nerve injury cannot be modulated by administration of a monoclonal antibody to CGRP. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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