Involvement of α₂‐adrenoceptors in inhibitory and facilitatory pain modulation processes

Abstract

These findings imply involvement of α2-adrenoceptors both in ipsilateral antinociceptive and pronociceptive pain modulation processes. However, a mechanism not involving α2-adrenoceptors appears to mediate analgesia in the ipsilateral forehead after HFS.

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

“…In rats, DNIC is affected by clinical doses of adrenergic agonists (e.g., dexmedetomidine and phenylephrine), suggesting an involvement of adrenergic neurons in DNIC (Sanada, Kohase, Makino, & Umino, 2009). Catecholamines like norepinephrine and epinephrine signal through the α2-adrenergic receptors (Vo & Drummond, 2016) concentrated in the spinal cord to produce an inhibitory effect. Neurons of the dorsal horn in the spinal cord are directly inhibited by serotonin (from serotoninergic neurons) which, through its action on facilitatory spinal 5-HT3 receptors, influences the expression of CPM (Bannister & Dickenson, 2017).…”

Effect of combined opioid receptor and α2-adrenoceptor blockade on anxiety and electrically evoked startle responses

“…Experiment 1 (administration of yohimbine) (Vo and Drummond, 2016) and Experiment 2 (co-administration of naltrexone and yohimbine) (Vo et al, 2016) were carried out sequentially, approximately one year apart. Both experiments followed a randomised, double-blind, placebo-controlled crossover design (i.e.…”

“…The sample for Experiment 1 consisted of 13 males and 10 females aged between 18–52 years (Vo and Drummond, 2016), and the sample for Experiment 2 consisted of 16 females aged between 18–32 years (Vo et al, 2016). Exclusion criteria included pregnancy, breast-feeding, chronic pain, psychiatric disorders, medical treatment for a condition that affected the heart, blood vessels, skin, liver or kidneys, or a known sensitivity to yohimbine and/or naltrexone.…”

“…We recently investigated the effects of yohimbine alone (Vo and Drummond, 2016) and co-administration of yohimbine and the opioid antagonist naltrexone (Vo et al, 2016) on various indices of pain in healthy human participants. In these studies, high frequency electrical stimulation (HFS) triggered hypersensitivity at and around the stimulated site in the forearm but inhibited pain more broadly, particularly on the ipsilateral side.…”

“…The R3 wave could form part of a startle response because it habituates rapidly and diminishes when the participant is forewarned about the stimulus (Ellrich et al, 1997, 2001). HFS potentiates R2, possibly due to increases in arousal, and this facilitatory effect is further augmented by yohimbine (Vo and Drummond, 2016). In the present study, it was hypothesised that drug administration (yohimbine, and co-administration of yohimbine with naltrexone) would strengthen R3, as these drugs boost anxiety and fear-potentiated startle responses (Davis, 1979; Davis et al, 1979; Kehne and Davis, 1985; Morgan et al, 1993; Stine et al, 2001).…”