The online version of this article (doi:10.1186/s12883-017-0839-9) contains supplementary material, which is available to authorized users.
In unilateral neuropathic pain. e.g. after peripheral nerve injury, both positive and negative sensory signs occur often, accompanied by minor but equally directed contralateral sensory changes. To mimic this feature, we experimentally aimed to induce concomitant c-fibre sensitization and block in healthy subjects and analyzed the bilateral sensory changes by quantitative sensory testing (QST) using the protocol of the German Research Network on Neuropathic Pain.
Twenty eight healthy subjects were firstly randomized in 2 groups to receive either topical capsaicin (0.6%, 12 cm2, application duration: 15 min.) or a lidocaine/prilocaine patch (25/25 mg, 10 cm2, application duration: 60 min.) on the right volar forearm. Secondly, 7–14 days later in the same area either at first capsaicin (for 15 min.) and immediately afterwards local anesthetics (for 60 min.) was applied (Cap/LA), or in inversed order with the same application duration (LA/Cap). Before, after each application and 7–14 days later a QST was performed bilaterally. Statistics: Wilcoxon-test, ANOVA, p < 0.05.
Single application of 0,6% capsaicin induced thermal hypoesthesia, cold hypoalgesia, heat hyperalgesia and tactile allodynia. Lidocaine/prilocaine alone induced thermal and tactile hypoesthesia as well as mechanical and cold hypoalgesia, and a heat hyperalgesia (to a smaller extent). Ipsilaterally both co-applications induced a combination of the above mentioned changes. Significant contralateral sensory changes occurred only after the co-application with concomitant sensitization and hypoesthesia and comprised increased cold (Cap/LA, LA/Cap) and mechanical detection as well as cold pain threshold (LA/Cap).
The present experimental model using combined application of capsaicin and LA imitates partly the complex sensory changes observed in patients with unilateral neuropathic pain and might be used as an additional surrogate model. Only the concomitant use both agents in the same area induces both positive and negative sensory signs ipsilaterally as well as parallel contralateral sensory changes (to a lesser extent).
ClinicalTrials.gov Identifier NCT01540877, registered on 23 February 2012.
Additional file 1: Table S1. A. QST data after single substance application (site of application; data are presented as median (range)). B. QST data after combined substance application (site of application; data are presented as median (range)). (DOCX 35 kb)
Additional file 2: Table S2. A. QST data after single substance application (contralateral to the application site; data are presented as median (range)). B. QST data after combined substance application (contralateral to the application site; data are presented as median (range)). (DOCX 34 kb)
Additional file 3: Figure S1. (A) Contralateral changes in the cold detection threshold of all subjects before and after application of a combination of capsaicin and local anesthetics as well as 7-14 days later. (B) Contralateral changes in the mechanical detection threshold of all subjects before and after application of capsaicin and local anesthetics as well as 7–14 days later. Gray circuits show the calculated group means. Red borders indicate significant changes. (TIF 1022 kb)
Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–73. CrossRefPubMedPubMedCentral
Maier C, Baron R, Tolle TR, Binder A, Birbaumer N, Birklein F, Gierthmuhlen J, Flor H, Geber C, Huge V, Krumova EK, Landwehrmeyer GB, Magerl W, Maihofner C, Richter H, Rolke R, Scherens A, Schwarz A, Sommer C, Tronnier V, Uceyler N, Valet M, Wasner G, Treede RD. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain. 2010;150(3):439–50. CrossRefPubMed
Baron R, Maier C, Attal N, Binder A, Bouhassira D, Cruccu G, Finnerup NB, Haanpää M, Hansson P, Hüllemann P, Jensen TS, Freynhagen R, Kennedy JD, Magerl W, Mainka T, Reimer M, Rice AS, Segerdahl M, Serra J, Sindrup S, Sommer C, Tölle T, Vollert J. Treede RD; German Neuropathic Pain Research Network (DFNS), and the EUROPAIN and NEUROPAINconsortia… Peripheral Neuropathic Pain: A mechanism-related organizing principle based on sensory profiles. Pain. 2017;158(2):261–72. CrossRefPubMed
Gierthmühlen J, Enax-Krumova EK, Attal N, Bouhassira D, Cruccu G, Finnerup NB, Haanpää M, Hansson P, Jensen TS, Freynhagen R, Kennedy JD, Mainka T, Rice A, Segerdahl M, Sindrup SH, Serra J, Tölle T, Treede RD, Baron R, Maier C. Who is healthy? Pain: Aspects to consider when including healthy volunteers in QST-based studies- a consensus statement by the EUROPAIN and NEUROPAIN consortia; 2015 [Epub ahead of print].
Rolke R, Baron R, Maier C, Tölle TR, Treede RD, Beyer A, Binder A, Birbaumer N, Birklein F, Bötefür IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magerl W, Maihöfner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123(3):231–43. CrossRefPubMed
Vollert J, Mainka T, Baron R, Enax-Krumova EK, Hüllemann P, Maier C, Pfau DB, Tölle T, Treede RD. Quality assurance for Quantitative Sensory Testing laboratories: development and validation of an automated evaluation tool for the analysis of declared healthy samples. Pain. 2015;156(12):2423–30. CrossRefPubMed
Sullivan MJL, Bishop SR, Pivik J. The Pain Catastrophizing Scale: Development and Validation. Psychol Assess. 1995;7(4):524–32. CrossRef
Gierthmühlen J, Maier C, Baron R, Tölle T, Treede RD, Birbaumer N, Huge V, Koroschetz J, Krumova EK, Lauchart M, Maihöfner C, Richter H. Westermann A; the German Research Network on Neuropathic Pain (DFNS) study group. Sensory signs in complex regional pain syndrome and peripheral nerve injury. Pain. 2012;153(4):765–74. CrossRefPubMed
Krause T, Asseyer S, Geisler F, Fiebach JB, Oeltjenbruns J, Kopf A, Villringer K, Villringer A, Jungehulsing GJ. Chronic sensory stroke with and without central pain is associated with bilaterally distributed sensory abnormalities as detected by Quantitative Sensory Testing. Pain. 2016;157(1):194–202. CrossRefPubMed
Shenker NG, Haigh RC, Mapp PI, Harris N, Blake DR. Contralateral hyperalgesia and allodynia following intradermal capsaicin injection in man. Rheumatology (Oxford). 2008;47(9):1417–21. CrossRef
- Ipsilateral and contralateral sensory changes in healthy subjects after experimentally induced concomitant sensitization and hypoesthesia
Elena K. Enax-Krumova
- BioMed Central