Interleukin-1 alpha has antiallodynic and antihyperalgesic activities in a rat neuropathic pain model.
Nerve injury and the consequent release of interleukins (ILs) are processes implicated in pain transmission. To study the potential role of IL-1 in the pathogenesis of allodynia and hyperalgesia, IL-1alpha and comparative IL-1beta, IL-6, and IL-10 mRNA levels were quantified using competitive RT-PCR of the lumbar spinal cord and dorsal root ganglia (DRG; L5-L6) three and seven days after chronic constriction injury (CCI) in rats. Microglial and astroglial activation in the ipsilateral spinal cord and DRG were observed after injury. In naive and CCI-exposed rats, IL-1alpha mRNA and protein were not detected in the spinal cord. IL-1beta and IL-6 mRNAs were strongly ipsilaterally elevated on day seven after CCI. In the ipsilateral DRG, IL-1alpha, IL-6, and IL-10 mRNA levels were increased on days three and seven; IL-1beta was elevated only on day seven. Western blot analysis revealed both the presence of IL-1alpha proteins (45 and 31 kDa) in the DRG and the down-regulation of these proteins after CCI. Intrathecal administration of IL-1alpha (50-500 ng) in naive rats did not influence nociceptive transmission, but IL-1beta (50-500 ng) induced hyperalgesia. In rats exposed to CCI, an IL-1alpha or IL-1 receptor antagonist dose-dependently attenuated symptoms of neuropathic pain; however, no effect of IL-1beta was observed. In sum, the first days after CCI showed a high abundance of IL-1alpha in the DRG. Together with the antiallodynic and antihyperalgesic effects observed after IL-1alpha administration, this finding indicates an important role for IL-1alpha in the development of neuropathic pain symptoms.
Mika
Joanna
J
Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
Korostynski
Michal
M
Kaminska
Dorota
D
Wawrzczak-Bargiela
Agnieszka
A
Osikowicz
Maria
M
Makuch
Wioletta
W
Przewlocki
Ryszard
R
Przewlocka
Barbara
B
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism* / Q000517:prevention & control*; D053582:Interleukin-1alpha / Q000008:administration & dosage* / Q000502:physiology / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D053582:Interleukin-1alpha