Transcutaneous electrical nerve stimulation (TENS) reduces chronic hyperalgesia induced by muscle inflammation Lisa Ainsworth a , Kendra Budelier a , Monica Clinesmith a , Abby Fiedler a , Rachel Landstrom a , B.J. Leeper a , LeAnn Moeller a , Sarah Mutch a , Kim O’Dell a , Jaclyn Ross a , Rajan Radhakrishnan a,b,1 , Kathleen A. Sluka a,b,c, * a Graduate Program of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa, IA, USA b Pain Research Program, University of Iowa, Iowa, IA, USA c Neuroscience Graduate Program, University of Iowa, Iowa, IA, USA Received 17 June 2005; received in revised form 21 October 2005; accepted 31 October 2005 Abstract Transcutaneous electrical nerve stimulation (TENS) reduces pain through central mechanisms involving spinal cord and brainstem sites. Since TENS acts through central mechanisms, we hypothesized that TENS will reduce chronic bilateral hyperalgesia produced by unilateral inflammation when applied either ipsilateral or contralateral to the site of muscle inflammation. Sprague–Dawley rats were injected with carrageenan in the left gastrocnemius muscle belly. Mechanical withdrawal threshold was tested bilaterally before and 2 weeks after carrageenan injection. After testing withdrawal thresholds at 2 weeks, rats received TENS treatment either ipsilateral or contralateral to the site of inflammation. In each of these groups, rats were randomized to control (no TENS), low frequency (4 Hz), or high frequency (100 Hz) TENS treatment. TENS was applied for 20 min at sensory intensity under light halothane anesthesia. Mechanical withdrawal thresholds were re-assessed after TENS or ‘no TENS’ treatment. Unilateral injection of carrageenan to the gastrocnemius muscle significantly reduced the mechanical withdrawal threshold (mechanical hyperalgesia) bilaterally 2 weeks later. Either low or high frequency TENS applied to the gastrocnemius muscle ipsilateral to the site of inflammation significantly reversed mechanical hyperalgesia, both ipsilateral and contralateral to the site of inflammation. Low or high frequency TENS applied to the gastrocnemius muscle contralateral to the site of inflammation also significantly reduced mechanical hyperalgesia, both ipsilateral and contralateral to the site of inflammation. Since ipsilateral or contralateral TENS treatments were effective in reducing chronic bilateral hyperalgesia in this animal model, we suggest that TENS act through modulating descending influences from supraspinal sites such as rostral ventromedial medulla (RVM). q 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Keywords: TENS; Hyperalgesia; Rat; Inflammation; Muscle; Carrageenan; Chronic 1. Introduction Chronic pain, especially musculoskeletal pain, is a widespread problem that often goes untreated due to lack of adequate treatment options, and also due to lack of understanding of alternative therapeutic modalities. Apart from pharmacological treatments, there are non-pharmaco- logical modalities, such as transcutaneous electrical nerve stimulation (TENS), which are clinically used to relieve pain. Despite a large number of preclinical studies, including some from our laboratory, the analgesic mechan- isms of TENS are not fully understood. Animal models of chronic musculoskeletal pain (Radhakrishnan et al., 2003a, b,c; Sluka et al., 2001) allow an experimental framework to determine the effectiveness and mechanisms of TENS in chronic pain. Pain 120 (2006) 182–187 www.elsevier.com/locate/pain 0304-3959/$20.00 q 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2005.10.030 * Corresponding author. Address: Graduate Program in Physical Therapy and Rehabilitation Sciences, The University of Iowa, 1-252 Medical Education Building, Iowa City, IA 52242-1190, USA. Tel.: C1 319 335 9791; fax: C1 319 335 9707. E-mail address: kathleen-sluka@uiowa.edu (K.A. Sluka). 1 Current address: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.