Role of peripheral polyamines in the development of inflammatory pain.

Abstract:

:Polyamines (putrescine, spermidine and spermine) are aliphatic amines that are produced by the action of ornithine decarboxylase (ODC) in a rate-limiting and protein kinase C (PKC)-regulated step. Because high levels of polyamines are found in the synovial fluid of arthritic patients, the aim of the present study was to identify the role of peripherally produced polyamines in a model of inflammatory pain induced by adjuvant. The subcutaneous injection of Complete Freund's adjuvant (CFA, 50 μL/paw) caused the development of mechanical allodynia and edema. Moreover, it increased ODC expression and activity and PKC activation. Administration of the selective ODC inhibitor DFMO (10 μmol/paw) attenuated the development of allodynia and edema and decreased ODC activity in both control and CFA-treated animals. Furthermore, administration of the PKC inhibitor GF109203X (1 nmol/paw) reduced allodynia and ODC activity in animals injected with CFA. A subcutaneous injection of putrescine (10 μmol/paw), spermidine (3-10 μmol/paw) or spermine (0.3-3 μmol/paw) into the rat paw also caused mechanical allodynia and edema. The present results suggest that endogenously synthesized polyamines are involved in the development of nociception and edema caused by an adjuvant. Moreover, polyamine production in inflammatory sites seems to be related to an increase in ODC activity stimulated by PKC activation. Thus, controlling polyamine synthesis and action could be a method of controlling inflammatory pain.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Silva MA,Klafke JZ,Rossato MF,Gewehr C,Guerra GP,Rubin MA,Ferreira J

doi

10.1016/j.bcp.2011.04.015

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

269-77

issue

3

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(11)00288-7

journal_volume

82

pub_type

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