Brief electrical stimulation of c-fibers in rats produces thermal hyperalgesia lasting weeks Jean-Jacques Vatine a , Ron Argov a , Ze’ev Seltzer b,c, * a Department of Physical Medicine and Rehabilitation, Hadassah University Hospital, Jerusalem, Israel b Physiology Branch, Faculty of Dental Medicine, Jerusalem, Israel c Department of Physiology, Faculty of Medicine, Hebrew University, Jerusalem, Israel Received 5 January 1998; received in revised form 2 March 1998; accepted 2 March 1998 Abstract Nerve injury produces neuropathic pain in some humans, but the nature of the signal triggering the pain is still unknown. When injured, many afferent fibers emit a prolonged discharge of action potentials. This input triggers pain disorders in rats following some, but not other types of total and partial nerve injury. In the present study we report that similar sensory disorders develop in rats by electrically stimulating an intact sciatic nerve. Robust thermal hyperalgesia and weak mechanical allodynia developed rapidly, lasting 3–5 weeks thereafter, but only when activating C-fibers. Thus, a discharge mimicking injury discharge in C-fibers, in the absence of any intended damage to the stimulated nerve, is sufficient to alter chronically central processing of sensory input.  1998 Elsevier Science Ireland Ltd. Keywords: Peripheral nerve stimulation; Injury discharge; Neuropathic pain; Allodynia; Hyperalgesia; Rat When a peripheral nerve is transected many sensory fibers emit a train of impulses, termed injury discharge (ID) [18]. ID usually lasts minutes, but in some fibers up to hours [1,3,11]. We and others reported that injury dis- charge is an important signal in triggering autotomy follow- ing total peripheral neurectomy. Blocking ID by a local anaesthetic suppressed autotomy expression [7,14], whereas artificially prolonging injury discharge by electrically sti- mulating C-fibers of the cut nerves, markedly increased levels of autotomy [14]. In addition, allodynia and hyper- algesia to thermal and mechanical stimuli were produced by injury discharge following chronic constriction injury of the sciatic nerve in the CCI model [2], but not following partial sciatic ligation in the PSL model [4]. In the present study we examined whether in the absence of any intended nerve damage, an artificial injury discharge produced by electrical stimulation of sciatic A- or A- and C-fibers, would produce in the rat lasting pain disorders. This study followed National regulations for humane ani- mal experimentation. The experiments were carried out on male Wistar rats (Harlan, Jerusalem) weighing 370–470 g at the time of operation. Under ether anesthesia and aseptic conditions, the sciatic nerve on both sides was carefully exposed at midthigh level, separating between the epineur- ium and neighboring tissues. A sheet of parafilm was placed under the nerves. A pair of stainless steel stimulating elec- trode hooks was inserted under the nerve on both sides, barely touching the epineurium. The exposed nerves were covered with mineral oil (37°C) to prevent damage by dry- ing. The side that received the tetanic stimulation alternated between rats. Electrical stimulation of the intact sciatic nerve on one side activated bilateral leg jerking, pulling the nerves by the hook electrodes. To prevent partial nerve injury by these jerks, both hindpaws, pelvis and tail were taped to the surgical board. In every rat we verified that the nerves were not pulled during stimulation by directly observing the surgical field using a dissecting microscope (25× magnification). In sham operated rats the sciatic nerve was exposed bilaterally and placed on stimulated electrodes for 10 min as described above. Rats were coded individually Neuroscience Letters 246 (1998) 125–128 0304-3940/98/$19.00  1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(98)00217-1 * Corresponding author. Department of Physiology, Faculty of Med- icine, Hebrew University, Jerusalem, POB 11720, 91120 Israel. Tel.: +972 2 6758611; fax: +972 2 6513180; e-mail: seltzer@cc.huji.ac.il