Exp Brain Res (2008) 189:1–10 DOI 10.1007/s00221-008-1399-4 123 RESEARCH ARTICLE EVects of NGF-induced muscle sensitization on proprioception and nociception Peter Svensson · Kelun Wang · Lars Arendt-Nielsen · Brian E. Cairns Received: 26 November 2007 / Accepted: 16 April 2008 / Published online: 14 May 2008 © Springer-Verlag 2008 Abstract Temporomandibular disorders (TMDs) are associated with perturbation of proprioceptive and noci- ceptive function. Recent studies have shown that injec- tion of the neurotrophic protein nerve growth factor (NGF) into the masseter muscle causes sensitization to mechanical pressure stimuli; however, it is not clear if vibration sense and jaw stretch reXexes as measures of proprioceptive function as well as glutamate-evoked pain are also altered. We tested the hypothesis that NGF- induced mechanical sensitization would be associated with changes in vibration sense and stretch reXex sensi- tivity as well as facilitation of glutamate-evoked pain responses. A double-blind, randomized and placebo- controlled study was conducted on 14 healthy men. In one session subjects received an injection of NGF (5 g in 0.2 ml) into the masseter muscle and in a control ses- sion an injection of buVered isotonic saline (0.9%, 0.2 ml). Subjects assessed their pain intensity on a 0–10 cm visual analogue scale (VAS) for 15 min after the injections. Pressure pain thresholds (PPT), vibration sense and jaw stretch reXexes were recorded at baseline and 1, 2, 3 and 24 h post-injection. The sensitivity to injections of glutamate into the masseter muscle (1 M, 0.2 ml) was assessed after 24 h. ANOVAs were used to assess signiWcant di Verences. NGF did not cause more pain than isotonic saline, but signiWcantly reduced PPTs 1, 2, 3 and 24 h post-injection (P < 0.001) whereas iso- tonic saline had no eVects on PPTs (P = 0.583). The injection of glutamate after 24 h was associated with reduced PPTs in both sessions, but the PPTs remained lower in the NGF pretreated masseter than in the control masseter (P < 0.001). Ratings of vibratory stimuli and the normalized amplitude of the jaw stretch reXex were not aVected by the NGF-induced sensitization; however, after glutamate injection a signiWcant increase in the stretch reXex was observed in the injected masseter mus- cle in both sessions (P = 0.002). There were no signiW- cant diVerences in the perceived pain intensity of the glutamate injection between the masseter muscle pre- treated with NGF or control (P > 0.414), although the glutamate-evoked pain drawing areas were larger for the NGF-pretreated masseter muscle (P = 0.009). In conclu- sion, this study con Wrms that masseter muscle injection of NGF is associated with a distinct and prolonged sen- sitization to mechanical stimuli, but without an eVect on large-diameter mechanoreceptive and the muscle spin- dle aVerents. Additional challenge of the NGF pretreated muscle with glutamate did not indicate a conspicuous sensitization to noxious chemical stimuli. These Wnd- ings are discussed in terms of the concept of “proprio- ceptive allodynia”. Keywords TMD pain · NGF · Stretch reXex · Proprioceptive allodynia P. Svensson (&) Department of Clinical Oral Physiology, School of Dentistry, University of Aarhus, Vennelyst Boulevard 9, 8000 Aarhus C, Denmark e-mail: psvensson@odont.au.dk P. Svensson Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, 8000 Aarhus C, Denmark P. Svensson · K. Wang · L. Arendt-Nielsen Orofacial Pain Laboratory, Center for Sensory–Motor Interaction, Aalborg University, 9220 Aalborg, Denmark B. E. Cairns Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, V6T 1Z3, Vancouver, Canada