Intrathecal urocortin I in the spinal cord as a murine model of stress hormone-induced musculoskeletal and tactile hyperalgesia.
Stress is antinociceptive in some models of pain, but enhances musculoskeletal nociceptive responses in mice and muscle pain in patients with fibromyalgia syndrome. To test the hypothesis that urocortins are stress hormones that are sufficient to enhance tactile and musculoskeletal hyperalgesia, von Frey fibre sensitivity and grip force after injection of corticotropin-releasing factor (CRF), urocortin I and urocortin II were measured in mice. Urocortin I (a CRF1 and CRF2 receptor ligand) produced hyperalgesia in both assays when injected intrathecally (i.t.) but not intracerebroventricularly, and only at a large dose when injected peripherally, suggesting a spinal action. Morphine inhibited urocortin I-induced changes in nociceptive responses in a dose-related fashion, confirming that changes in behaviour reflect hyperalgesia rather than weakness. No tolerance developed to the effect of urocortin I (i.t.) when injected repeatedly, consistent with a potential to enhance pain chronically. Tactile hyperalgesia was inhibited by NBI-35965, a CRF1 receptor antagonist, but not astressin 2B, a CRF2 receptor antagonist. However, while urocortin I-induced decreases in grip force were not observed when co-administered i.t. with either NBI-35965 or astressin 2B, they were even more sensitive to inhibition by astressin, a non-selective CRF receptor antagonist. Together these data indicate that urocortin I acts at CRF receptors in the mouse spinal cord to elicit a reproducible and persistent tactile (von Frey) and musculoskeletal (grip force) hyperalgesia. Urocortin I-induced hyperalgesia may serve as a screen for drugs that alleviate painful conditions that are exacerbated by stress.
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue Room 295, St Paul, MN, 55108, USA.
Alice A
AA
Larson
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue Room 295, St Paul, MN, 55108, USA.
Myra G
MG
Nunez
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue Room 295, St Paul, MN, 55108, USA.
Casey L
CL
Kissel
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue Room 295, St Paul, MN, 55108, USA.
Katalin J
KJ
Kovács
D000073:Acenaphthenes / Q000008:administration & dosage; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D018737:Hand Strength; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology*; D007278:Injections, Spinal; D051379:Mice; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement; D010446:Peptide Fragments / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000008:administration & dosage; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects*; D013315:Stress, Psychological / Q000139:chemically induced* / Q000150:complications; D054832:Urocortins / Q000008:administration & dosage*; D000099052:CRF Receptor, Type 1
C504986:6-cyclopropylmethyl-2-(2,4-dichlorophenyl)-7-ethyl-4-methyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene; D000073:Acenaphthenes; C101531:CRF receptor type 2; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C528574:astressin-2B; C518358:urocortin 2, mouse; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
corticosterone; corticotropin-releasing hormone; glucocorticoids; grip force; pain