title: Role of CB1 and CB2 cannabinoid receptors in the development of joint pain induced by monosodium iodoacetate.
abstract: Joint pain is a common clinical problem for which both inflammatory and degenerative joint diseases are major causes. The purpose of this study was to investigate the role of CB1 and CB2 cannabinoid receptors in the behavioral, histological, and neurochemical alterations associated with joint pain. The murine model of monosodium iodoacetate (MIA) was used to induce joint pain in knockout mice for CB1 (CB1KO) and CB2 cannabinoid receptors (CB2KO) and transgenic mice overexpressing CB2 receptors (CB2xP). In addition, we evaluated the changes induced by MIA in gene expression of CB1 and CB2 cannabinoid receptors and μ-, δ- and κ-opioid receptors in the lumbar spinal cord of these mice. Wild-type mice, as well as CB1KO, CB2KO, and CB2xP mice, developed mechanical allodynia in the ipsilateral paw after MIA intra-articular injection. CB1KO and CB2KO demonstrated similar levels of mechanical allodynia of that observed in wild-type mice in the ipsilateral paw, whereas allodynia was significantly attenuated in CB2xP. Interestingly, CB2KO displayed a contralateral mirror image of pain developing mechanical allodynia also in the contralateral paw. All mouse lines developed similar histological changes after MIA intra-articular injection. Nevertheless, MIA intra-articular injection produced specific changes in the expression of cannabinoid and opioid receptor genes in lumbar spinal cord sections that were further modulated by the genetic alteration of the cannabinoid receptor system. These results revealed that CB2 receptor plays a predominant role in the control of joint pain manifestations and is involved in the adaptive changes induced in the opioid system under this pain state.
authors.affiliation: Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, C/Dr. Aiguader, 88, 08003 Barcelona, Spain Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Av. Ramon y Cajal, s/n, 03550, San Juan de Alicante, Alicante, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: La Porta
authors.forename: Simona Andreea
authors.initials: SA
authors.lastname: Bura
authors.forename: Auxiliadora
authors.initials: A
authors.lastname: Aracil-Fernández
authors.forename: Jorge
authors.initials: J
authors.lastname: Manzanares
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
mesh_terms: D000818:Animals; D018771:Arthralgia / Q000139:chemically induced / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007270:Injections, Intra-Articular; D019807:Iodoacetic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009619:Nociceptors / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000502:physiology*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D013116:Spinal Cord / Q000502:physiology
chemical_list: C578453:CNR1 protein, mouse; C571431:Cnr2 protein, mouse; D004791:Enzyme Inhibitors; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019807:Iodoacetic Acid