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Fructose‐1,6‐bisphosphate reduces inflammatory pain‐like behaviour in mice: role of adenosine acting on A 1 receptors
Author(s) -
Valério DA,
Ferreira FI,
Cunha TM,
AlvesFilho JC,
Lima FO,
De Oliveira JR,
Ferreira SH,
Cunha FQ,
Queiroz RH,
Verri Jr WA
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00325.x
Subject(s) - adenosine , hyperalgesia , adenosine a3 receptor , cytokine , adenosine receptor , cxcl1 , adenosine a1 receptor , pharmacology , chemistry , medicine , nociception , endocrinology , receptor , chemokine , agonist
Background and purpose: D‐Fructose‐1,6‐bisphosphate (FBP) is an intermediate in the glycolytic pathway, exerting pharmacological actions on inflammation by inhibiting cytokine production or interfering with adenosine production. Here, the possible antinociceptive effect of FBP and its mechanism of action in the carrageenin paw inflammation model in mice were addressed, focusing on the two mechanisms described above. Experimental approach: Mechanical hyperalgesia (decrease in the nociceptive threshold) was evaluated by the electronic pressure‐metre test; cytokine levels were measured by elisa and adenosine was determined by high performance liquid chromatography. Key results: Pretreatment of mice with FBP reduced hyperalgesia induced by intraplantar injection of carrageenin (up to 54%), tumour necrosis factor α (40%), interleukin‐1 β (46%), CXCL1 (33%), prostaglandin E 2 (41%) or dopamine (55%). However, FBP treatment did not alter carrageenin‐induced cytokine (tumour necrosis factor α and interleukin‐1 β) or chemokine (CXCL1) production. On the other hand, the antinociceptive effect of FBP was prevented by systemic and intraplantar treatment with an adenosine A 1 receptor antagonist (8‐cyclopentyl‐1,3‐dipropylxanthine), suggesting that the FBP effect is mediated by peripheral adenosine acting on A 1 receptors. Giving FBP to mice increased adenosine levels in plasma, and adenosine treatment of paw inflammation presented a similar antinociceptive mechanism to that of FBP. Conclusions and implications: In addition to anti‐inflammatory action, FBP also presents an antinociceptive effect upon inflammatory hyperalgesia. Its mechanism of action seems dependent on adenosine production but not on modulation of hyperalgesic cytokine/chemokine production. In turn, adenosine acts peripherally on its A 1 receptor inhibiting hyperalgesia. FBP may have possible therapeutic applications in reducing inflammatory pain.