Changes induced by formalin pain in central α1- adrenoceptor density are modulated by adenosine receptor agonists

Irena Nalepa, Jerzy Vetulani, Valentina Borghi, Marta Kowalska, Barbara Przewłocka, Adam Roman, Flaminia Pavone

Research output: Contribution to journalArticlepeer-review


We aimed to elucidate the role of α1-adrenoceptors in adenosine analgesia in the formalin test. Formalin was injected into the hind paw of male CD-1 mice after injection of adenosine A1 or A 2a receptor agonists, CPA, [N(6)-cyclopentyladenosine], and CGS21680 [2-p-(2-carboxyethyl)-phenylethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride]. In the behavioral experiment, α1-adrenoceptors were blocked by an α1-adrenoceptor antagonist prazosin, 0.01 mg/kg i.p., and the time mice spent paw licking was recorded for the early (0-15 min) and late (15-60 min) phase of formalin pain. In the neurochemical experiments, mice were killed 15 or 45 min after formalin injection. The density of α1-adrenoceptors was assessed in various brain areas and in the lumbar spinal cord by [3H]prazosin autoradiography. Adenosine agonists produced analgesia in both phases of formalin pain, while prazosin showed a tendency to pronociceptive action in the late phase, and antagonized the effect of CGS21680. After formalin injection, α1- adrenoceptor density was elevated in some brain areas, mainly in the late phase (some contralateral amygdaloid and ipsilateral thalamic nuclei) and depressed in others (early phase in the ipsilateral spinal cord and late phase in both ipsi- and contralateral sensorimotor cortex). Elevation of α1- adrenoceptor density, which may be interpreted as a defensive response, did not develop in several cases of CPA-pretreated mice. This suggests that the analgesic effect of adenosine A1 receptor activation renders the defensive response unnecessary. The depression of α1- adrenoceptors may suggest development of hypersensitivity in a given structure, and this was antagonized by CGS21680, suggesting the role of A2a receptors in control of inflammatory formalin pain.

Original languageEnglish
Pages (from-to)549-558
Number of pages10
JournalJournal of Neural Transmission
Issue number5
Publication statusPublished - May 2010


  • Adenosine
  • Alpha(1)-adrenoceptor
  • Autoradiography
  • Inflammatory pain
  • Prazosin

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health


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