Neuroscience Letters 583 (2014) 55–59 Contents lists available at ScienceDirect Neuroscience Letters jo ur nal ho me page: www.elsevier.com/locate/neulet Nociceptive sensitization and BDNF up-regulation in a rat model of traumatic brain injury David P. Feliciano a , Peyman Sahbaie b , Xiaoyou Shi a,b , Michael Klukinov a , J. David Clark a,b,∗ , David C. Yeomans a a Department of Anesthesiology Perioperative and Pain Medicine, 291 Campus Drive, Stanford, CA 94305, United States b Anesthesiology Service, VA Palo Alto Healthcare System, 3801 Miranda Avenue, Palo Alto, CA 94304, United States h i g h l i g h t s • Mild TBI was induced in rats using fluid percussion. • Nociceptive assessment demonstrated little change in hindpaw thermal thresholds. • Mild TBI rats did demonstrate mechanical allodynia contralateral to the TBI lesions. • Lumbar spinal cord levels of BDNF were elevated contralateral to TBI at both the mRNA and protein levels. a r t i c l e i n f o Article history: Received 7 August 2014 Received in revised form 9 September 2014 Accepted 11 September 2014 Available online 20 September 2014 Keywords: Traumatic brain injury Chronic pain Brain derived neurotrophic factor a b s t r a c t Chronic pain after traumatic brain injury (TBI) is very common, but the mechanisms linking TBI to pain experienced in the periphery have not been described. In this set of studies we examined nociceptive sensitization and changes in spinal cord gene expression using the rat lateral fluid percussion model of mild TBI. We did not identify changes in thermal nociceptive thresholds in rats with mild TBI. However, mechanical allodynia in hind paws contralateral to TBI was significant and sustained. We also found that spinal cord levels of brain derived neurotrophic factor (BDNF) but not several other pain-related genes were up-regulated one week after injury. Our findings suggest that TBI-induced up-regulation of spinal BDNF levels might contribute to chronic TBI-related pain, and that the lateral fluid percussion model might be useful for exploring this relationship. Published by Elsevier Ireland Ltd. 1. Introduction Traumatic brain injury (TBI) frequently occurs in battlefield, motor vehicle and sports-related injuries and is accompanied by a high rate of chronic pain [19]. For example, a history of TBI con- fers an odds ratio of 5.0 for chronic pain amongst US veterans [10]. Chronic pain in the setting of TBI contributes to suffering, complicates rehabilitative efforts and poses a significant overall challenge to management teams. Unfortunately very little informa- tion is available concerning effective approaches to the treatment of chronic pain in the setting of TBI, and our current analgesic Abbreviations: CCI, controlled cortical impact; LFP, lateral fluid percussion; PTSD, post-traumatic stress disorder; TBI, traumatic brain injury; NSS, neurological sever- ity score. ∗ Corresponding author at: Anesthesiology Service, VA Palo Alto Healthcare Sys- tem, 3801 Miranda Avenue, Palo Alto, CA 94304, United States. Tel.: +1 650 493 5000; fax: +1 650 852 3423. E-mail address: djclark@stanford.edu (J.D. Clark). armamentarium has many shortcomings when used to treat TBI patients. Though commonly used, opioids are associated with med- ication abuse issues that are especially problematic for young TBI patients [9]. Alternatively, non-steroidal anti-inflammatory drugs (NSAIDS), are substantially less potent and are associated with poorer TBI outcomes [2]. Clearly there is a large need for improved pain relief for patients with TBI and chronic pain. The prevalence of chronic pain in TBI patients has been exam- ined in several studies involving civilian and military cohorts. The most commonly reported painful areas include the head, spine, and limbs, with the overall prevalence ranging from 22 to 95% depend- ing on the pain site [19], though additional injuries may be involved. Interactions between TBI and the prevalence and severity of chronic pain have been demonstrated [10,19]. In a group of patients with relatively late-onset pain, the symptoms were noted to be greater on the side contralateral to injury implying that damage to spe- cific centers or neural pathways may be involved [21,22]. Testing of the painful limbs of these late onset TBI patients demonstrated mechanical allodynia consistent with changes in pain processing http://dx.doi.org/10.1016/j.neulet.2014.09.030 0304-3940/Published by Elsevier Ireland Ltd.