Prevaccination with diluted Freund adjuvant prevents the development of chronic pain and transient release of cerebrospinal fluid substance P in adjuvant-induced arthritis in rats.
Parallel time courses of preclinical and behavioural pain-related parameters and levels of substance P-like immunoreactivity in plasma (plasma-SPLI) and cerebrospinal fluid (CSF-SPLI) were studied in 2 groups of rats injected with an arthritogenic solution (concentrated Freund adjuvant) over a 9-week post-infection (PI) period; 1 group was pretreated with saline (control) and 1 pretreated with diluted Freund adjuvant (immunized). In control rats all symptoms of adjuvant-induced arthritis (AIA) developed while in immunized rats AIA symptoms were significantly reduced or did not appear. A significant increase in plasma-SPLI was obvious as early as the 2nd week PI and remained at this level in both groups of animals until the end of the 9-week PI observation period, but with a significantly higher increase in control versus immunized group at all stages. In contrast, CSF-SPLI transiently peaked only in the control group at 3 weeks PI whereas CSF-SPLI values did not differ from one week to another in both groups of rats. These results suggest that successive injections of diluted Freund adjuvant impairs the development of chronic inflammation and pain in AIA in rats, as well as the transient increase in SP release in CSF at 3 weeks PI, but not the long-lasting increased SP release in plasma. Since there is a clear dissociation between our biochemical and preclinical and behavioral data, this study does not provide evidence for the role of substance P as a possible biologic marker of chronic pain either in plasma or in CSF.(ABSTRACT TRUNCATED AT 250 WORDS)
Calvino
B
B
INSERM U161, Unité de Recherches de Physiopharmacologie du Système Nerveux, 75014 ParisFrance Université Paris XII-Val de Marne, CréteilFrance Service de Pharmacologie et d'Immunologie, DSV/DRIPP, Commissariat à l'Energie Atomique, Centre d'Etudes Nucléaires / Saclay, 91000 Gif sur Yvette Cedex and Université Paris VII, Paris Cedex 05 France.
Couraud
J Y
JY
Besson
J M
JM
D000818:Animals; D001169:Arthritis, Experimental / Q000134:cerebrospinal fluid / Q000473:pathology / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D002908:Chronic Disease; D005620:Freund's Adjuvant / Q000627:therapeutic use*; D006614:Hindlimb / Q000473:pathology; D009043:Motor Activity / Q000502:physiology; D010146:Pain / Q000517:prevention & control* / Q000523:psychology; D010147:Pain Measurement; D051381:Rats; D013373:Substance P / Q000097:blood / Q000134:cerebrospinal fluid*; D014611:Vaccination; D014828:Vocalization, Animal / Q000502:physiology
D013373:Substance P; D005620:Freund's Adjuvant