Cr Bohotin

Preconditioning with cobalt chloride modifies pain perception in mice.

Cobalt chloride (CoCl2) modifies mitochondrial permeability and has a hypoxic-mimetic effect; thus, the compound induces tolerance to ischemia and increases resistance to a number of injury types. The aim of the present study was to investigate the effects of CoCl2 hypoxic preconditioning for three weeks on thermonociception, somatic and visceral inflammatory pain, locomotor activity and coordination in mice. A significant pronociceptive effect was observed in the hot plate and tail flick tests after one and two weeks of CoCl2 administration, respectively (P<0.001). Thermal hyperalgesia (Plantar test) was present in the first week, but recovered by the end of the experiment. Contrary to the hyperalgesic effect on thermonociception, CoCl2 hypoxic preconditioning decreased the time spent grooming the affected area in the second phase of the formalin test on the orofacial and paw models. The first phase of formalin-induced pain and the writhing test were not affected by CoCl2 preconditioning. Thus, the present study demonstrated that CoCl2 preconditioning has a dual effect on pain, and these effects should be taken into account along with the better-known neuro-, cardio- and renoprotective effects of CoCl2.

Glyceryl trinitrate has opposite effects on different experimental models of pain

IntroductionThe actions of glyceryl trinitrate (GTN) are the result ofits bioconversion into NO; NO increases the intracellu-lar concentration of cyclic guanosine monophosphate(cGMP), which produces pain modulation in the centraland peripheral nervous system (Griesberger et al. 2011,).In addition, GTN administration is considered a reliableexperimental model of migraine, based on the neuronaleffects on the integrative-nociceptive structures (deTommaso et al. 2004).Purposeto investigate the effects of GTN 4 hours after itsadministration on different experimental pain models inmice.MethodsSixteen Swiss male mice were divided into 2 groups:control group (n=8) and GTN group (n=8, 10 mg/kg b.w. i.p ). Assessment of locomotor activity (activity cage)and nociceptive tests (tailflick-TF and hot plate-HP)were performed before GTN administration and consid-ered as baseline. Four hours after GTN injection, loco-motor activity assessment and nociceptive tests were re-evaluated; afterwards, 20 I¼l of 5% formalin were admi-nistrated into the upper right lip in order to assess for-malin-induced orofacial pain. The results werecompared with paired and unpaired Student’s t test.ResultsGTN administration significantly increased HP latencies(p=0.0002) and showed a tendency towards increasing TF(p=0.056). A decrease in the locomotor activity was notedfor both vertical movement activity (-78% p =0.001) aswell as horizontal movement activity (-87% p=0.0001).GTN had no significant effect in influencing formalin-induced orofacial pain response.ConclusionIn our study GTN administration in mice exerted analge-sic effects on acute nociception but had no effect on orofa-cial formalin pain. In addition, GTN decreased locomotoractivity. Taken together, our results demonstrate thattrigeminal pain is differently modulated by GTN as com-pared to nociception in TF and HP.

The effects of intrathecal methylene blue and glyceryl trinitrate administration on orofacial pain in mice

Methods: 24 BALB/c mice were divided in 3 groups as follows: GTN group (0.1mg/kg, n=8), MB group (0.05mg/kg, n=8) and control group (NaCl, n=8). All groups received the substances intrathecally. Two hours after drug/saline administration, formalin was injected into the upper lip and the time mice spent rubbing/liking the injected area was recorded. The results for each phase are presented in seconds. ANOVA and Dunnett post-hoc test were used for statistical evaluation.

Repeated methylene blue administration produces analgesia in experimental pain

Methylene blue (MB), a widely used inhibitor of NO activity/production, is also a reduction-oxidation agent that can act both as a powerful antioxidant and as an enhancer of the electron transport chain. Furthermore, it prevents formation of mitochondrial oxygen free radicals and promotes oxygen consumption ( Atamna et al. 2010 , Rojas et al. 2012 ).

Chronic cobalt exposure modifies nociception and orofacial inflammatory pain

Cobalt chloride (CoCl2) is a widely used hypoxia-mimetic; preconditioning with cobalt has been reported to exert protection against ischemic injury as well as decreasing pro-inflammatory cytokine levels ( Shukla et al. 2011 ). Exposure to moderate hypoxia may lead to neurological phenomena such as paraesthesia, numbness or pain, possibly as a consequence of the modifications that appear in small DRG neurones. ( Gruss et al. 2006 ).