Asymmetric Lateralization during Pain Processing

Pain is defined as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”. This complex perception arises from the coordinated activity of several brain areas processing either sensory–discriminative or affective–motivational components. Functional studies performed in healthy volunteers revealed that affective–emotional components of pain are processed bilaterally but present a clear lateralization towards the right hemisphere, regardless of the site of stimulation. Studies at the cellular level performed in experimental animal models of pain have shown that neuronal activity in the right amygdala is clearly pronociceptive, whilst activation of neurons in the left amygdala might even exert antinociceptive effects. A shift in lateralization becomes evident during the development of chronic pain; thus, in patients with neuropathic pain symptoms, there is increased activity in ipsilateral brain areas related with pain. These observations extend the asymmetrical left–right lateralization within the nervous system and provide a new hypothesis for the pathophysiology of chronic forms of pain. In this article, we will review experimental data from preclinical and human studies on functional lateralization in the brain during pain processing, which will help to explain the affective disorders associated with persistent, chronic pain.

[1]  J. Hsieh,et al.  Neuronal correlates of gastric pain induced by fundus distension: a 3T‐fMRI study , 2004, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[2]  I. Tracey Imaging pain , 2019, Journal of the Neurological Sciences.

[3]  G. Schwartz,et al.  Differential lateralization for positive versus negative emotion , 1979, Neuropsychologia.

[4]  Yarimar Carrasquillo,et al.  Hemispheric lateralization of a molecular signal for pain modulation in the amygdala , 2008, Molecular pain.

[5]  S. Waxman,et al.  Pain Perception: Multiple Matrices or One? , 2016, JAMA neurology.

[6]  J. Kehr,et al.  Asymmetry of the endogenous opioid system in the human anterior cingulate: a putative molecular basis for lateralization of emotions and pain. , 2015, Cerebral cortex.

[7]  D. Finn,et al.  The effect of pain on cognitive function: A review of clinical and preclinical research , 2011, Progress in Neurobiology.

[8]  J. Maisog,et al.  Pain intensity processing within the human brain: a bilateral, distributed mechanism. , 1999, Journal of neurophysiology.

[9]  R. Peyron,et al.  Pain matrices and neuropathic pain matrices: A review , 2013, PAIN®.

[10]  R. Coghill,et al.  Hemispheric lateralization of somatosensory processing. , 2001, Journal of neurophysiology.

[11]  C. Woods,et al.  Congenital Insensitivity to Pain Overview , 1993 .

[12]  M. Gazzaniga,et al.  Pain perception in a man with total corpus callosum transection , 1989, Pain.

[13]  H. Flor,et al.  Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations , 2017, Nature Reviews Neurology.

[14]  Michael B. First,et al.  Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11) , 2019, Pain.

[15]  L. Arendt-Nielsen,et al.  Understanding Pain Catastrophizing: Putting Pieces Together , 2020, Frontiers in Psychology.

[16]  C. Gauriau,et al.  Pain Pathways and Parabrachial Circuits in the Rat , 2002, Experimental physiology.

[17]  Robert C. Coghill,et al.  The Distributed Nociceptive System: A Framework for Understanding Pain , 2020, Trends in Neurosciences.

[18]  V. Neugebauer,et al.  The Amygdala and Persistent Pain , 2004, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[19]  R. Peyron,et al.  Mechanical allodynia in neuropathic pain. Where are the brain representations located? A positron emission tomography (PET) study , 2013, European journal of pain.

[20]  Harley J. Bobnar,et al.  Left and right hemispheric lateralization of the amygdala in pain , 2020, Progress in Neurobiology.

[21]  D. Bouhassira,et al.  Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. , 2006, Brain : a journal of neurology.

[22]  T. Schnitzer,et al.  Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. , 2013, Brain : a journal of neurology.

[23]  A. M. Watabe,et al.  Predominant synaptic potentiation and activation in the right central amygdala are independent of bilateral parabrachial activation in the hemilateral trigeminal inflammatory pain model of rats , 2018, Molecular pain.

[24]  N. Costes,et al.  Haemodynamic brain responses to acute pain in humans: sensory and attentional networks. , 1999, Brain : a journal of neurology.

[25]  V. Neugebauer Amygdala physiology in pain. , 2020, Handbook of behavioral neuroscience.

[26]  J. Besson,et al.  The organization of the efferent projections from the pontine parabrachial area to the amygdaloid complex: A phaseolus vulgaris leucoagglutinin (PHA‐L) study in the rat , 1993, The Journal of comparative neurology.

[27]  M. Bushnell,et al.  Pain perception: is there a role for primary somatosensory cortex? , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Nakia S. Gordon,et al.  Right-lateralized pain processing in the human cortex: an FMRI study. , 2006, Journal of neurophysiology.

[29]  Michael R Bruchas,et al.  Endogenous and Exogenous Opioids in Pain. , 2018, Annual review of neuroscience.

[30]  R. Schmidt,et al.  GABA and Glycine in Spinal Nociceptive Processing , 2013 .

[31]  H. Bastuji,et al.  Pain networks from the inside: Spatiotemporal analysis of brain responses leading from nociception to conscious perception , 2016, Human brain mapping.

[32]  H. Bastuji,et al.  Pain and consciousness , 2017, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[33]  R. Treede,et al.  Human brain mechanisms of pain perception and regulation in health and disease , 2005, European journal of pain.

[34]  V. Neugebauer,et al.  Hemispheric lateralization of pain processing by amygdala neurons. , 2009, Journal of neurophysiology.

[35]  Clifford J. Woolf,et al.  Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment , 2019, Neuron.

[36]  U Salvolini,et al.  Mechanical noxious stimuli cause bilateral activation of parietal operculum in callosotomized subjects. , 2002, Cerebral cortex.

[37]  B. Kolber,et al.  Divergent functions of the left and right central amygdala in visceral nociception , 2017, Pain.

[38]  K. Amunts,et al.  A short review on emotion processing: a lateralized network of neuronal networks , 2021, Brain structure & function.

[39]  T. Satterthwaite,et al.  Engaging endogenous opioid circuits in pain affective processes , 2020, Journal of neuroscience research.

[40]  D. Yurgelun-Todd,et al.  The right-hemisphere and valence hypotheses: could they both be right (and sometimes left)? , 2007, Social cognitive and affective neuroscience.

[41]  Krish D. Singh,et al.  fMRI of Thermal Pain: Effects of Stimulus Laterality and Attention , 2002, NeuroImage.

[42]  L. Obler,et al.  Right hemisphere emotional perception: evidence across multiple channels. , 1998, Neuropsychology.

[43]  Peter Svensson,et al.  A PET activation study of brush-evoked allodynia in patientswith nerve injury pain , 2006, Pain.

[44]  H. Bastuji,et al.  Convergence of sensory and limbic noxious input into the anterior insula and the emergence of pain from nociception , 2018, Scientific Reports.

[45]  D. Goldberg,et al.  Pain as a global public health priority , 2011, BMC public health.

[46]  H. Flor,et al.  The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. , 2020, Pain.

[47]  P. Rainville,et al.  Ipsilateral cortical representation of tactile and painful information in acallosal and callosotomized subjects , 2008, Neuropsychologia.