Preconditioning with cobalt chloride modifies pain perception in mice

Abstract

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.

Intracerebroventricular Coadministration of Protoxin-II and Trace Elements in Rats Enhances the Analgesic Effect of the 1.7 Voltage-Gate Sodium Channel Blocker

“…Animals were supervised daily and removed from the study if any neurological deficits were noted, if there was a weight loss greater than >15% over 3 days, or if the cannulas were obstructed. e behavioural tests, hot plate (HPT), tail flick (TF), and paw withdrawal thresholds (PWTs), have been performed using a protocol presented previously by our group [4,5]. In the ICV administration, all reagents were freshly diluted in 10 μL of saline.…”

“…Behavioural procedures were performed by a researcher blinded to team and treatment. Considering the principles of the 3Rs (Replacement, Reduction, and Refinement) for performing more humane animal research, we selected the doses of Cd, Mg, and Zn after extensive literature study on the use of trace elements as analgesics or coanalgesics [4][5][6][7][14][15][16][17][18][19][20][21][22][23], and the selection was refined according to Sutoo and Akiyama [14] to obtain optimal balance between efficacy and safety.…”

“…Moreover, coadministration of Mg and tramadol has revealed an important improvement of tramadol's analgesic activity as measured by the hot-plate and tail-flick tests [4]. Previous studies [4,5] also revealed a significant analgesic effect for cadmium chloride mostly on visceral pain as assessed with the writhing test.…”

“…e evaluation through thermonociceptive tests of three diverse doses of magnesium chloride (37.5, 75, and 150 mg/kg) in a murine acute pain model showed direct antinociceptive effects [5]. Moreover, coadministration of Mg and tramadol has revealed an important improvement of tramadol's analgesic activity as measured by the hot-plate and tail-flick tests [4]. Previous studies [4,5] also revealed a significant analgesic effect for cadmium chloride mostly on visceral pain as assessed with the writhing test.…”

“…erefore, it is a constant need to discover novel molecules that target diverse pain pathways, with an improved safety profile and better treatment adherence. In the past decade, a variety of in vitro/in vivo and clinical reports have centred on reviewing the use of common trace elements as analgesics or coanalgesics that increase the medication effects, thus leading to improved pain management or smaller dosage demands [2][3][4][5].…”