Central sensitization in the trigeminal nucleus caudalis produced by a conjugate of substance P and the A subunit of cholera toxin.
Individuals with chronic craniofacial pain experience symptoms that are consistent with central sensitization. In fact, central sensitization may constitute the major disease process in these conditions, particularly if the original injury has healed or the condition is idiopathic. To understand central sensitization we have developed a conjugate of substance P and cholera toxin (SP-CTA). SP-CTA is selectively taken up by cells that express neurokinin receptors. Twenty-four hours following intracisternal administration of SP-CTA, wild-type rats and mice demonstrated signs of persistent background nociception, but when tested for facial cold sensitivity, they did not differ from controls. However, treating the SP-CTA-injected animals with naloxone exposed cold hypersensitivity in the face. Mu-opioid receptor knockout mice treated with SP-CTA demonstrated hypersensitivity without naloxone treatment. These findings suggest that central sensitization leads to activation of an endogenous opioid system. The data also demonstrate that the intracisternal administration of SP-CTA in rodents is a useful model for studying central sensitization as a disease process without having to induce a peripheral injury.


CONCLUSIONS
Central sensitization is a concern in many craniofacial pain conditions. In this project, we utilize a conjugate of substance P and the catalytic subunit of cholera toxin to induce central sensitization in the nucleus caudalis of rodents. The data indicate that the injected animals become hypersensitive in the face.
Caudle
Robert M
RM
Department of Oral and Maxillofacial Surgery, University of Florida College of Dentistry, Gainesville, Florida, USA. caudle@ufl.edu
King
Christopher
C
Nolan
Todd A
TA
Suckow
Shelby K
SK
Vierck
Charles J
CJ
Neubert
John K
JK
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002772:Cholera Toxin / Q000494:pharmacology* / Q000627:therapeutic use; D002946:Cisterna Magna; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005157:Facial Pain / Q000188:drug therapy; D005260:Female; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement; D051381:Rats; D054772:Rats, Hairless; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology; D013373:Substance P / Q000494:pharmacology* / Q000627:therapeutic use; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects*
D017450:Receptors, Opioid, mu; D013373:Substance P; D002772:Cholera Toxin