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GABAA receptor Gamma- aminobutyric acid type B receptor N-type calcium channel Adenylate cyclase type 2 G protein- activated inward rectifier potassium channel 1 Substance-P receptor Kappa-type opioid receptor Gβ Guanine nucleotide- binding protein G(i) subunit alpha-1 Gγ γ-Aminobutyric acid Substance P Meperidine cAMP Ca+ Ca+ Na+ Na+ γ-Aminobutyric acid Meperidine Meperidine ATP PPi GTP Pain Magnesium Less GABA leads to disinhibition of dopamine cell firing in the spinal chord pain transmission neurons. This leads to less pain signalling and analgesia Decreased calcium levels lead to decreased neurotransmitter release. Less GABA is released for synaptic vesicles. Meperidine activates presynaptic kappa opioid type receptors in the dorsal root ganglion The Gi subunit of the Kappa opioid receptor activates the inwardly rectifying potassium channel increasing K+ conductance. This causes membrane hyperpolarization decreasing the chances of neuronal firing/action potential. Post-Synaptic Neuron Pre-Synaptic Neuron Synapse Cytosol Synaptic Vesicle The kappa opioid receptor through the gamma subunit inhibits voltage gated N-type calcium channels stopping the influx of calcium into the neuron. Meperidine acts at A delta and C pain fibres in the dorsal horn of the spinal chord. By decreasing neurotransmitter action there is less pain transmittance into the spinal chord. This leads to less pain perception. C Pain Fibres Substance P as well as acetylcholine and noradrenaline have a direct effect on nociceptor firing. Therefore less of these neurotransmitters leads to less firing of the neuron which leads to less pain signalling. The inhibition of adenylate cyclase prevents the production of cAMP which further prevents depolarization and pain signalling
GABRG2 GABBR1 CACNA1B ADCY2 KCNJ3 TACR1 OPRK1 GNB1 GNAI1 GNG2 γ-Aminobutyric acid Substance P Meperidine cAMP Calcium Calcium Sodium Sodium γ-Aminobutyric acid Meperidine Meperidine Adenosine triphosphate Pyrophosphate Guanosine triphosphate Pain
GABRG2 GABBR1 CACNA1B ADCY2 KCNJ3 TACR1