US EPA

1515152 

Journal Article 

Subcutaneous formalin produces centrifugal hyperalgesia at a non-injected site via the NMDA-nitric oxide cascade 

Wiertelak, EP; Furness, LE; Horan, R; Martinez, J; Maier, SF; Watkins, LR 

1994 

Yes 

Brain Research
ISSN: 0006-8993
EISSN: 1872-6240 

649 

1-2 

19-26 

English 

7953632 

10.1016/0006-8993(94)91044-8 

WOS:A1994NU98600004 

http://://WOS:A1994NU98600004
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Previous work has demonstrated that pain facilitation can occur following injection of subcutaneous irritants, such as formalin. Such studies have focused on apparent pain facilitation induced at the site of irritant injection. Changes in processing of incoming pain information have typically been assumed to result from activation of neurocircuitry intrinsic to the spinal cord. The present series of studies have examined hyperalgesia exhibited at a site distant from the site of irritant injection and have begun to define the neurocircuitry and neuropharmacology underlying this pain enhancement. This work demonstrates that s.c. formalin injected into the dorsum of one hindpaw in rats produces prolonged hyperalgesia as measured by the tailflick test. Hyperalgesia is not mediated solely by circuitry intrinsic to the spinal cord, but rather involves activation of centrifugal pathways originating within the brain and descending to the spinal cord via pathway(s) outside of the dorsolateral funiculus. At the level of the spinal cord, this hyperalgesic state is mediated by an NMDA-nitric oxide cascade, since hyperalgesia can be abolished by administration of either an NMDA antagonist (APV) or a nitric oxide synthesis inhibitor (L-NAME). 

2-Amino-5-phosphonovalerate/pharmacology; Animals; Arginine/analogs & derivatives/pharmacology; Cordotomy; Formaldehyde/administration & dosage; Hot Temperature; Hyperalgesia/ chemically induced/physiopathology; Injections, Spinal; Injections, Subcutaneous; N-Methylaspartate/antagonists & inhibitors/ physiology; NG-Nitroarginine Methyl Ester; Nitric Oxide/antagonists & inhibitors/ physiology; Pain Measurement/drug effects; Rats, Sprague-Dawley; Spinal Cord/physiology