title: Arthritic calcitonin/alpha calcitonin gene-related peptide knockout mice have reduced nociceptive hypersensitivity.
abstract: Peripheral inflammation induced with a knee joint injection of a mixture of kaolin/carrageenan (k/c) produces primary and secondary hyperalgesia. Inflammatory pain is thought to involve a variety of transmitters released from nerve terminals, including amino acids, substance P (SP) and calcitonin gene-related peptide (CGRP). In the present study, mice deficient in the calcitonin/alpha CGRP gene (CGRP(-/-)) displayed normal responses to noxious stimuli. However, the CGRP knockout mice failed to demonstrate development of secondary hyperalgesia after induction of knee joint inflammation in two tests that assess central sensitization, through testing at sites remote from the primary insult. Nociceptive behavioral responses were assessed using the hot-plate test and paw withdrawal latency (PWL) to radiant heat applied to the hindpaw. The CGRP(-/-) mice showed no signs of secondary hyperalgesia after development of knee joint inflammation, while the expected significant decrease in the PWL was observed in the CGRP(+/+) mice as control. The CGRP(-/-) mice also had a prolonged rather than a shortened response latency in the hot-plate test 4 h after knee joint injection of k/c. Immunohistological study showed that CGRP-like immunoreactivity (CGRP-LI) was absent in the spinal cord and dorsal root ganglia taken from the CGRP(-/-) mice. These results indicate that endogenous CGRP plays an important role in the plastic neurogenic changes occurring in response to peripheral inflammatory events including the development of nociceptive behaviors.
authors.affiliation: Department of Anatomy and Neurosciences, The University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555-1069, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: A O
authors.initials: AO
authors.lastname: Hoff
authors.forename: S J
authors.initials: SJ
authors.lastname: Wimalawansa
authors.forename: G J
authors.initials: GJ
authors.lastname: Cote
authors.forename: R F
authors.initials: RF
authors.lastname: Gagel
authors.forename: K N
authors.initials: KN
authors.lastname: Westlund
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D002116:Calcitonin / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D006358:Hot Temperature; D007150:Immunohistochemistry; D007596:Joints / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement; D011930:Reaction Time
chemical_list: D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide