Calcium-permeable channels control intracellular calcium dynamics in both neuronal and nonneuronal cells to orchestrate sensory functions including pain. Calcium entering the cell throughout these channels is associated with transduction, transmission, processing, and modulation of pain signals. Clinic, genetic, biochemical, biophysical and pharmacological evidence points toward calcium-permeable channels as the key players in acute and persistent pain conditions. Ligand-gated calcium channels such as TRP channels or some subtypes of voltage-gated calcium channels shows abnormal functioning in persistent pain states. Also, NMDA receptors can be unlocked from their physiological Mg 2+ blockade under persisten pain states to culminate with central sensitization. The primary goal of this chapter is to present an overview of the functioning of different classes of calcium-permeable channels and how they become altered to modulate the sensation of pain in acute and chronic states. The most important evidence from classical and recent studies will be discussed trying to depict ways of modulating those channels as a strategy for better pain control.
Combining drugs with different mechanisms of action results in additive and/or synergic effects providing thus opioid-sparing strategies in pain management. This studydetermines the antinociceptive interaction after intravenous co-administration of ketamine and lidocaine in rat models of acute and inflammatory pain and evaluates the effect of the combination on motor activity. Thermal pain is accessed by tail-flick. Inflammatory pain is induced bycompound Freund adjuvant (CFA) into the right hind paw. Mechanical allodynia is assessed with von-Frey filaments. Motoreffects are evaluated by rotarod apparatus.The profile of interaction is assessed by Isobolographic analysis. Ketamine and lidocaine, alone or in combination, dose-dependently ameliorate acute thermal pain and mechanical allodynia triggered by CFA. The dose of combinationthat reach 20% or 50% of the maximum possible effect is lower than the expected for an additive interaction suggesting, thus,synergism. The interaction indexes are 0.001 and 0.029 for thermal and inflammatory pain, respectively. Ketamine alone but not in combination reduces the motor performance in the rotarod at 50% antinociceptive dose. Combined ketamine and lidocaine synergistically attenuates thermal and inflammatory pain. Therefore, smaller doses of both drugs retain their analgesic efficacy and are associated with lower alterations in motor activity.
Fentanyl induced a hyperalgesic effect and was not inhibited by ketamine, lidocaine, and ascorbic acid in rats. Observations show that large doses of opioids may increase postoperative pain.
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