Effects of peripheral inflammation on activation of p38 mitogen-activated protein kinase in the rostral ventromedial medulla

• Published in: Brain research Vol. 1134; no. 1; pp. 131 - 139
• Main Authors: Imbe, Hiroki, Okamoto, Keiichiro, Aikawa, Fumiko, Kimura, Akihisa, Donishi, Tomohiro, Tamai, Yasuhiko, Iwai-Liao, Yasutomo, Senba, Emiko
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 23.02.2007; Amsterdam Elsevier; New York, NY
• Subjects: Adjuvants, Immunologic; Afferent Pathways - enzymology; Animals; Biological and medical sciences; Cell Count; Descending system; Enzyme Activation - physiology; Foot - innervation; Foot - physiopathology; Hyperalgesia; Immunohistochemistry; Inflammation; Inflammation - enzymology; Inflammation - physiopathology; Inflammation Mediators; Male; Medical sciences; Medulla Oblongata - anatomy & histology; Medulla Oblongata - enzymology; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuronal Plasticity - physiology; Nociceptors - enzymology; p38 MAPK; p38 Mitogen-Activated Protein Kinases - metabolism; Pain - enzymology; Pain - physiopathology; Raphe Nuclei - anatomy & histology; Raphe Nuclei - enzymology; Rats; Rats, Sprague-Dawley; Reticular Formation - anatomy & histology; Reticular Formation - enzymology; Serotonin - metabolism; Tryptophan Hydroxylase - metabolism; complete Freund's adjuvant; extracellular signal-regulated kinase; Gi; OX42; AMPA; vanilloid receptor type 1 of the transient receptor potential channel family; JNK; N-methyl- d-aspartate; NRM; RVM; MAPK phosphatase; phosphate buffer; PFA; spinal trigeminal nucleus; nucleus lateralis paragigantocellularis; neuronal nuclei; BSA; Tris-buffered saline; brain-derived neurotrophic factor; paraformaldehyde; c-Jun N-terminal kinase; nucleus raphe magnus; TBS; LPGi; long-term depression; rostral ventromedial medulla; nucleus reticularis gigantocellularis pars alpha; MAPK; p38 MAPK; NeuN; 7; glial fibrillary acidic protein; LTD; bovine serum albumin; CFA; ERK; RT; room temperature; TPH; Hyperalgesia; mitogen-activated protein kinase; Descending system; NMDA; tryptophan hydroxylase; Sp5; BDNF; CD11b-Rat macrophages/microglial cells; TBST; facial nucleus; Inflammation; TRPV1; alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate; GFAP; PB; MKP; nucleus reticularis gigantocellularis; PAG; periaqueductal gray matter; TBS containing 0.1% Triton X-100; GiA; Nervous system diseases; Rat; Enzyme; Rodentia; Central nervous system; Mitogen-activated protein kinase; Activation; Encephalon; Vertebrata; Mammalia; Animal; Medulla oblongata
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.11.091

Abstract In the present study, the activation of p38 mitogen-activated protein kinase (p38 MAPK) in the rostral ventromedial medulla (RVM) following the injection of complete Freund's adjuvant (CFA) into the rat hindpaw was examined in order to clarify the mechanisms underlying the dynamic changes in the descending pain modulatory system after peripheral inflammation. Phospho-p38 MAPK-immunoreactive (p-p38 MAPK-IR) neurons were observed in the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (GiA). Inflammation induced the activation of p38 MAPK in the RVM, with a peak at 30 min after the injection of CFA into the hindpaw, which lasted for 1 h. In the RVM, the number of p-p38 MAPK-IR neurons per section in rats killed at 30 min after CFA injection (19.4 ± 2.0) was significantly higher than that in the naive group (8.4 ± 2.4) [ p < 0.05]. At 30 min after CFA injection, about 40% of p-p38 MAPK-IR neurons in the RVM were serotonergic neurons (tryptophan hydroxylase, TPH, positive) and about 70% of TPH-IR neurons in the RVM were p-p38 MAPK positive. The number of p-p38 MAPK- and TPH-double-positive RVM neurons in the rats with inflammation was significantly higher than that in naive rats [ p < 0.05]. These findings suggest that inflammation-induced activation of p38 MAPK in the RVM may be involved in the plasticity in the descending pain modulatory system following inflammation.