title: Long-lasting hyperalgesia and sympathetic dysregulation after formalin injection into the rat hind paw.
abstract: Subcutaneous formalin injection has been used extensively to evaluate acute effects (over several hours) of chemical nociceptive stimulation on nociceptive reflexes. Also, a persistent hyperreflexia for mechanical and thermal stimulation, lasting 3 weeks after formalin injection, has been revealed and related to microglial activation in the spinal dorsal horn. The present study demonstrates more prolonged effects of formalin injection, lasting 6 weeks, on operant escape from nociceptive thermal stimulation. Operant escape requires cerebral processing of nociceptive input and can detect effects that are not limited to spinal or spinal-brain stem-spinal reflex circuits. Compared with rats injected with saline, escape responding to 44.5 degrees C and 47 degrees C stimulation was increased after bilateral s.c. injection of 5% formalin into the dorsal hind paws. The hyperalgesia outlasted visible signs of trauma (e.g. paw edema). Responses to 36 degrees C were not altered after formalin injection, providing a control for effects of the peripheral injury on activity levels or exploratory tendencies. Skin temperature recordings from the forepaws and contralateral hind paw during 44.5 degrees C stimulation of the left hind paw provided an indirect measure of cutaneous blood flow in formalin- and saline-injected animals. Normal reductions in skin temperature during thermal stimulation were attenuated (nearly eliminated) at 1 and 2 weeks after formalin injection and partially recovered by 10 weeks. Thus, formalin-induced tissue injury produced a long-term secondary hyperalgesia, accompanied by a reduced sympathetic responsivity. The similar time-course for these phenomena suggests that there are mechanistic linkages between focal injury, autonomic dysregulation and enhanced pain sensitivity.
authors: Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610-0244, USA. vierck@mbi.ufl.edu
authors: C J
authors: CJ
authors: Vierck
authors: R P
authors: RP
authors: Yezierski
authors: A R
authors: AR
authors: Light
mesh_terms: D000818:Animals; D020211:Autonomic Dysreflexia / Q000139:chemically induced / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced* / Q000523:psychology; D001831:Body Temperature / Q000187:drug effects; D003627:Data Interpretation, Statistical; D005260:Female; D005528:Foot; D005557:Formaldehyde / Q000008:administration & dosage; D006614:Hindlimb; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000523:psychology; D007267:Injections; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D005557:Formaldehyde