Abstract
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.
Highlights
The fact that persistent pain is commonly associated with depression and an2xoife1t0y disorder, while fear and stress typically inhibit pain, is a fascinating dichotomy that stresses the fundamental and complex relationship between emotional and sensory tahsepefuctnsdinampeanintapl earncedpctioomn.pAlelxthroeulagthiolnastheripalibzeattwioenenduerminogtipoanianl parnodcessesninsogrhyaassnpoetctbseienn peaxitnenpseivrceelyptsiotund. iAedlt,htohuegfhielladteorfalaifzfaetcitoinvednueriunrgospcaieinncperohcaesssdienbgahteads nfoort dbeecandeexstehnoswivethlye sbtruadiniedp,rtohceesfiseelsd eomf aoftfieocntisv,eannedurtowscoiemncaejohrasthdeeobraietesdofforcedreecbardaelslahtoewratlihzeatbiroaninhparvoecebsesesn epmrooptioosnesd,.aTnhdetw“roigmhtajhoermthisepohrierseohf ycperoetbhreaslisla”tesruagligzeasttisonthhaatveemboeteinonpsroapreosperde.dTohmein“raingthlyt hpermociesspsheedreinhytphoethreigsihst” shuegmgiesspthsetrheatreemgaortdiolensssaoref pthreediromafifneacntitvlye pvraolceenscseed(pinostihtievreigvhst
(STT) and the spino-parabrachial-amygdala (PB) pathways. These precise targets have been assessed in non-human primates following the pathways marked by stained herpes viruses, which upon injection at the dorsal horn of the spinal ctoridnfaercet tthranlasmpoicrtperdojreocstitoranllnyeutoroinfse, catntdhafrloamitchpereojoenctioodnifnfeurernotncso, ratnicdalfraoremasthbeyrme oeanntos doifftfrearnensstycnoarptitciacltarraenasspboyrtm[1e2a]n. s of transsynaptic transport [12]
Patients with a severed corpus-callosum are able to detect nociceptive stimuli applied unilaterally [28,29]; they showed bilateral activation of pain-related brain areas, regardless of the stimulated side [30,31], supporting the idea that the activation of both hemispheres does not depend exclusively on cortical connections, and most likely relies on direct peripheral inputs (Figure 2 depicts the anatomical substrate for ipsilateral connectivity)
Summary
The fact that persistent pain is commonly associated with depression and an2xoife1t0y disorder, while fear and stress typically inhibit pain, is a fascinating dichotomy that stresses the fundamental and complex relationship between emotional and sensory tahsepefuctnsdinampeanintapl earncedpctioomn.pAlelxthroeulagthiolnastheripalibzeattwioenenduerminogtipoanianl parnodcessesninsogrhyaassnpoetctbseienn peaxitnenpseivrceelyptsiotund. iAedlt,htohuegfhielladteorfalaifzfaetcitoinvednueriunrgospcaieinncperohcaesssdienbgahteads nfoort dbeecandeexstehnoswivethlye sbtruadiniedp,rtohceesfiseelsd eomf aoftfieocntisv,eannedurtowscoiemncaejohrasthdeeobraietesdofforcedreecbardaelslahtoewratlihzeatbiroaninhparvoecebsesesn epmrooptioosnesd,.aTnhdetw“roigmhtajhoermthisepohrierseohf ycperoetbhreaslisla”tesruagligzeasttisonthhaatveemboeteinonpsroapreosperde.dTohmein“raingthlyt hpermociesspsheedreinhytphoethreigsihst” shuegmgiesspthsetrheatreemgaortdiolensssaoref pthreediromafifneacntitvlye pvraolceenscseed(pinostihtievreigvhst. This pathway is related with the affective and motivational components inherent to pain perception [18] and constitutes the “second-order” network, which includes sections of the anterior insula (AI), anterior mid-cingulate (aMCC), lateral prefrontal, and posterior parietal areas. According to the scientific literature (see above), the innervation of many brain areas is bilateral, providing an anatomical substrate for two-sided processing that would allow for functional lateralization.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
