Tehran University of Medical Sciences Current Journal of Neurology 2717-011X 13 1 2014 03 15 19 27 Zahra Alizadeh Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. Masoud Fereidoni Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. Morteza Behnam-Rassouli Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. Shirin Hosseini Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. 2015 10 14 Background: Usual dosage  of morphine  (10 mg/kg) induces  analgesia  and ultra-low dose (ULD) of morphine (1 μg/kg); hyperalgesia, and  C-fibers are also bearing  μ- opioid receptors; here the importance  of C-fibers on pain and  morphine   induced  analgesia/hyperalgesia  is questioned   and  investigated    using   pain   evaluation methods and infant capsaicin treating  for C-fibers lesioning. Methods: Wistar   male   rats   (200-250   grams)   were assigned  to three  categories  i.e. control, sham (receiving neonatal    capsaicin vehicle) and  c-lesion   (receiving neonatal  capsaicin), each one  with three  groups  (n = 7). They were injected intraperitoneally with single dosage of saline, 10 mg/kg or 1 μg/kg morphine, respectively. Thermal pain threshold  was evaluated  using the tail flick test before and 30 minutes  after the injections. Chemical pain was assessed using the formalin test (FT) 30 minutes after the administrations. Results: Results:  indicated  that  thermal  (P < 0.001) and chemical  pains  in  both neurogenic and inflammatory phases  of FT (P < 0.05) were reduced  in C-lesion animals. In the C-normal and C-lesion animals, 10 mg/kg morphine exerted analgesia  both  in thermal  (P < 0.001) and  two phases of FT (P < 0.01), but it was more potent in C-lesion animals (P < 0.05). Although ULD of morphine in C-normal animals  produced  hyperalgesic effect in thermal and chemical pains (P < 0.001), in C-lesion animals, it produced analgesia (P < 0.05) at the neurogenic phase of FT. Conclusion: Results can raise the C-fibers involvement for a significant portion of nociceptive transmission, because C-lesioning potentiated morphine  induced analgesia and eliminated ULD of morphine induced hyperalgesia.Therefore C and  Aδ fibers can be  involved in morphine analgesia; while, just C-fibers are possibly responsible  for only presynaptically hyperalgesic/excitatory action of ULD in morphine. https://ijnl.tums.ac.ir/index.php/ijnl/article/view/629 https://ijnl.tums.ac.ir/index.php/ijnl/article/download/629/173