The Effect of Oral Morphine on Pain-Related Brain Activation - An Experimental Functional Magnetic Resonance Imaging Study

Abstract

Knowledge about cerebral mechanisms underlying pain perception and effect of analgesic drugs is important for developing methods for diagnosis and treatment of pain. The aim was to explore altered brain activation before and after morphine treatment using functional magnetic resonance imaging recorded during experimental painful heat stimulation. Functional magnetic resonance imaging data were recorded and analysed in 20 healthy volunteers (13 men and 7 women, 24.9 AE 2.6 years) in a randomized, double-blind, placebo-controlled, cross-over study. Painful stimulations were applied to the right forearm using a contact heat evoked potential stimulator (CHEPS) before and after treatment with 30 mg oral morphine and placebo. CHEPS stimulations before treatment induced activation in the anterior cingulate cortex, secondary somatosensory cortex/insula, thalamus and cerebellum (n = 16, p < 0.05). In response to morphine treatment, the spatial extent of these pain-specific areas decreased (n = 20). Reduced pain-induced activation was seen in the right insula, anterior cingulate cortex and inferior parietal cortex after morphine treatment compared to before treatment (n = 16, p < 0.05), and sensory ratings of pain perception were significantly reduced after morphine treatment (p = 0.02). No effect on pain-induced brain activation was seen after placebo treatment compared to before treatment (n = 12, p > 0.05). In conclusion, heat stimulation activated areas in the 'pain matrix' and a clinically relevant dose of orally administered morphine revealed significant changes in brain areas where opioidergic pathways are predominant. The method may be useful to investigate the mechanisms of analgesics.

Characterization of cortical source generators based on electroencephalography during tonic pain

“…Studies have shown that these areas are not unique for nociception but also present a reflection of non-nociceptive-specific cognitive processes elicited by nociceptive stimulation 31,32. However, these areas were selected as most previous studies have shown a consistent activation during different pain stimuli and across various imaging and electrophysiological modalities 11,16,33,34. This validates the method used in the present study.…”

Differential effects of oxycodone and venlafaxine on resting state functional connectivity—A randomized placebo‐controlled magnetic resonance imaging study

“…Moreover, ACC and insula are regions well known to be important in pain processing . Increased functional connectivity between ACC and insula during rest has been demonstrated in chronic pain conditions, and in an acute pain model, we showed increased activity in ACC, insula, and thalamus in healthy volunteers, whereas morphine (mu‐opioid receptor agonist) decreased activity in insula, ACC, and inferior parietal cortex . Even in absence of painful stimulation, we demonstrated in the present study that oxycodone decreased functional connectivity in these brain regions.…”

Morphine Attenuates fNIRS Signal Associated With Painful Stimuli in the Medial Frontopolar Cortex (medial BA 10)

“…For example, in preclinical studies using electrophysiological measures of neural activation produced by painful stimuli, morphine was reported to inhibit neuronal activity to pain evoked in a number of these regions including the S1, thalamus (the ventral posterolateral nucleus and the mediodorsal nucleus), and ACC (Wang et al, 2009 ). In human imaging studies, inhibitive effects of morphine on the pain-induced cortical activations were previously seen in the ACC, the insula and the inferior parietal cortex (Becerra et al, 2006 ; Hansen et al, 2015 ). To date, little data is available on the modulation of morphine on brain deactivations or on BA 10 response associated with pain.…”