Differential effects of K+ channel blockers on antinociception induced by α2‐adrenoceptor, GABAB and κ‐opioid receptor agonists

Ocaña, María; Baeyens, José M.

doi:10.1111/j.1476-5381.1993.tb13919.x

Cited by 60 publications

(31 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Potassium channels modulate the drug-induced antinociception. For example, K ATP openers potentiate morphine or tricyclic antidepressant-induced analgesia in mice, while blockers which are devoid of analgesic properties do not seem to modify significantly morphine antinociception (Ocana and Baeyens, 1993;Ocana et al, 1996;). These observations are in good agreement with the absence of analgesic effects of TEA, ChTX, and GLI as observed in the present work.…”

Section: Discussionmentioning

confidence: 99%

Antisense Knockdown of the Shaker-like Kv1.1 Gene Abolishes the Central Stimulatory Effects of Amphetamines in Mice and Rats

Ghelardini

Quattrone

Galeotti

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

Amphetamine (AMPH) is an indirect sympathomimetic compound classified as a substrate-type releaser that distinguishes it from other stimulants that act as uptake 1 blockers, such as cocaine (COC). In mammals, AMPH elicits central stimulation, hypermotility, anorexia, analgesia and analeptic activity, mainly through the increase of extracellular brain dopamine (DA). The inversion of vesicular transporters and/or intravesicular alkalinization is assumed to have a role in AMPH-induced exocytosis. However, the action mechanism of this compound has not yet been completely clarified. Recent evidence on the action of AMPHs indicates potassium channel-blocking properties in peripheral tissues. We investigated the possible involvement of a Shaker-like Kv1.1 channel subtype in the central effects of AMPH, using an antisense oligodeoxyribonucleotide (aODN) that specifically and reversibly inhibits the expression of these channels in the brain. The effect of aODN pretreatments was studied by evaluating the modification of behavioral effects induced in mice through the intracerebroventricular administration of AMPH, COC, or other compounds. The aODN in mice almost completely blocked the stimulatory effects of AMPH and other releasers but was ineffective in reducing the central activity of COC. In aODN-pretreated rats a strong reduction of the AMPH, but not of the COC-stimulated DA efflux from nucleus accumbens was observed. Our results suggest that the stimulant effects of AMPH and chemically related compounds, but not COC, require the presence of functionally active Kv1.1 channels in the brain.

show abstract

Section: Discussionmentioning

confidence: 99%

Antisense Knockdown of the Shaker-like Kv1.1 Gene Abolishes the Central Stimulatory Effects of Amphetamines in Mice and Rats

Ghelardini

Quattrone

Galeotti

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Further studies found that the antinociceptive effect of NE is mediated by α 2 -adrenoceptors (Howe et al 1983;Fleetwood-Walker et al 1985;Yaksh 1985). The activation of α 2 -adrenoceptors increases potassium conductance in dorsal horn neurons, which produces hyperpolarization and decreases excitability, thereby contributing to analgesia (North and Yoshimura, 1984;Ocana and Baeyens, 1993;Grudt et al, 1995). On the other hand, α 2 -adrenoceptor agonists reduce the stimulus-evoked release of substance P (Kuraishi et al, 1985;Pang and Vasko, 1986) and glutamate (Kamisaki et al, 1993;Ueda et al, 1995) in the spinal cord, thus suppressing nociceptive transmission.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal α-adrenoceptors

Koo

Lim

Chung

et al. 2008

Pain

View full text Add to dashboard Cite

In a previous study, we showed that electroacupuncture (EA) applied to the SI-6 point on the contralateral forelimb produces long-lasting and powerful analgesia in pain caused by ankle sprain in a rat model. To investigate the underlying mechanism of EA analgesia, the present study tested the effects of various antagonists to known endogenous analgesic systems in this model. Ankle sprain was induced in anesthetized rats by overextending their right ankle with repeated forceful plantar flexion and inversion of the foot. When rats developed pain behaviors (a reduction in weight bearing of the affected hind limb), EA was applied to the SI-6 point on the contralateral forelimb for 30 minutes under halothane anesthesia. EA significantly improved the weight-bearing capacity of the affected hind limb for 2 hours, suggesting an analgesic effect. The alpha-adrenoceptor antagonist phentolamine (2 mg/kg, i.p. or 30 μg, i.t.) completely blocked the EA-induced analgesia, whereas naloxone (1 mg/kg, i.p.) and failed to block the effect. These results suggest that EA-induced analgesia is mediated by alpha-adrenoceptor mechanisms. Further experiments showed that intrathecal administration of yohimbine (10 μg), an α 2 -adrenergic antagonist, reduced the EAinduced analgesia in a dose-dependent manner, whereas terazosin (10 μg), an α 1 -adrenergic antagonist, did not produce any effect. These data suggest that the analgesic effect of EA in ankle sprain pain is, at least in part, mediated by spinal α 2 -adrenoceptor mechanisms.

show abstract

“…Early work indicated that K ATP may mediate the analgesic effects of morphine (Ocana et al 1990) or clonidine (Ocana et al 1993) since the antinociceptive effects of these agents could be reversed by pretreatment with glibenclamide, a selective K ATP antagonist. Recent studies indicate that glibenclamide can antagonize the antinociceptive effects of a variety of compounds such as nitric oxide and cyclic GMP in an assortment of animal models of nociception, such as those wherein hyperalgesia is produced by carrageenan or prostaglandin E 2 (PGE 2 ) (Rodrigues and Duarte 2000;Soares et al 2001;Alves and Duarte, 2002).…”

Section: Introductionmentioning

confidence: 99%

ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

2007

View full text Add to dashboard Cite

Behavioral studies have shown that the hyperalgesia arising from inflammatory agents, such as prostaglandin E 2 (PGE 2 ) can be antagonized by activators of the ATP-sensitive potassium current (K ATP ). This observation raises questions as to whether this suppression results from a direct action on sensory neurons and what are the cellular mechanisms giving rise to this inhibition. We found that small to medium diameter sensory neurons isolated from the L4-6 DRGs expressed the mRNAs for Kir6.1, Kir6.2, and SUR1. In perforated-patch clamp recordings from acutely dissociated sensory neurons from the young adult rat, exposure to 300 μM diazoxide, a K ATP channel agonist, significantly hyperpolarized the resting membrane potential, reduced the number of action potentials evoked by a ramp of depolarizing current, and increased the amplitude of inward K ATP currents evoked by the voltage ramp. Similar results were obtained with the protonophore FCCP, which is known to reduce the levels of intracellular ATP and lead to the activation of K ATP . Only a subpopulation of sensory neurons was sensitive to diazoxide whereas other neurons were unaffected. Treatment with 1 μM PGE 2 significantly enhanced the excitability of these small to medium diameter capsaicin-sensitive sensory neurons; this enhancement was reversed by subsequent exposure to diazoxide in a subpopulation of neurons. Similar to diazoxide, exposure to 8-Br-cyclic GMP antagonized the PGE 2 -induced increase in excitability. The effects of 8-Br-cyclic GMP could be reversed by exposure to glibenclamide, an antagonist of K ATP channels. As with diazoxide, only a subpopulation of sensory neurons were affected by 8-Br-cyclic GMP. These results demonstrate that activation of K ATP can reverse the sensitization produced by PGE 2 and may be an important means to modulate the enhanced excitability that results from inflammatory or injury conditions.

show abstract

Differential effects of K⁺ channel blockers on antinociception induced by α₂‐adrenoceptor, GABA_B and κ‐opioid receptor agonists

Cited by 60 publications

References 30 publications

Antisense Knockdown of the Shaker-like Kv1.1 Gene Abolishes the Central Stimulatory Effects of Amphetamines in Mice and Rats

Antisense Knockdown of the Shaker-like Kv1.1 Gene Abolishes the Central Stimulatory Effects of Amphetamines in Mice and Rats

Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal α-adrenoceptors

ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

Contact Info

Product

Resources

About