Pain and Decision-Making: Interrelated Through Homeostasis
Celina A. Salcido, Maxine K. Geltmeier, Perry N. Fuchs*
Department of Psychology, The University of Texas Arlington, Arlington, TX 76019-0528, USA
Pain is a multidimensional experience that motivates organisms to engage in behavioral repertoire to deal with potential life-threatening situations that are a threat to homeostatic function. The aim of this mini-review was to highlight the nature of pain, the role that pain has as a motivational drive to impact higher-order cognitive processes, such as decision making, and how these processes are intimately integrated with homeostatic mechanisms.
Both conceptual and neurobiological overlap suggest a close interaction of decision-making, pain, and homeostasis. Pain, decision-making and homeostasis are interconnected through a common denominator of survival and must be considered when assessing pain-related issues and treatments.
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* Address correspondence to this author at the Department of Psychology, University of Texas at Arlington, 313 Life Science Building, Box 19528, 501 S. Nedderman Drive, Arlington, TX 76019-0528, USA; Tel: + 1 817 272 2281; Fax: (817) 272 2364; E-mail: firstname.lastname@example.org.
Pain and Decision-Making: Interrelated Through Homeostasis
Homeostasis is an ongoing auto-regulatory process in the body that maintains a relatively steady internal psychological and physiological equilibrium despite acting external forces and is exclusively for survival [1Cannon WB. Organization for physiological homeostasis. Physiol Rev 1929; 9(3): 399-431. [http://dx.doi.org/10.1152/physrev.1918.104.22.1689] ]. A stable state is required for optimal functioning of an organism and is dependent on autonomic, neuroendocrine, and behavioral regulatory mechanisms that are tightly interconnected. Each of these regulatory mechanisms buffers changes in the environment or within the body through cascading responses from each of these systems to restore imbalances [2Kotas ME, Medzhitov R. Homeostasis, inflammation, and disease susceptibility. Cell 2015; 160(5): 816-27.https://www.sciencedirect.com/ science/article/pii/ S0092867415001750 [http://dx.doi.org/10.1016/j.cell.2015.02.010] [PMID: 25723161] -4McEwen BS. Allostasis and allostatic load: Implications for neuropsychopharmacology. Neuropsychopharmacology 2000; 22(2): 108-24. [http://dx.doi.org/10.1016/S0893-133X(99)00129-3] [PMID: 10649824] ]. Thus, these mechanisms are biological and unconscious in nature, working in an organized and hierarchical manner to revert to a balanced state. Yet, the homeostatic activity can also be a function of tangible behavior, motivating an organism to relieve distress and promote survival. Typical homeostatic motivational drives such as hunger and thirst are often used as classic examples. In recent years, however, the importance of ongoing auto-regulatory processes related to the motivational drive of pain is also being recognized [5Craig AD. A new view of pain as a homeostatic emotion 2003; 26: 303-7.http://www.sciencedirect.com. ezproxy.uta.edu/science/ article/pii/S0166223603001231-8Rainville P. Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol 2002; 12(2): 195-204.http://www.ncbi.nlm.nih.gov/ pubmed/12015237 [http://dx.doi.org/10.1016/S0959-4388(02)00313-6] [PMID: 12015237] ]. Therefore, the purpose of this paper is to highlight the importance of pain as a motivational drive that directs behavior and ultimately impacts higher-order cognitive processes, such as decision making, via interrelated homeostatic processes.
1.1. Multidimensionality of Pain
Similar to other motivational drives that have a multidimensional experience, pain is often regarded as a subjective and universal phenomenon that has biological, psychological, and social implications [9Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull 2007; 133(4): 581-624.http://www.ncbi.nlm.nih.gov/ pubmed/17592957 [http://dx.doi.org/10.1037/0033-2909.133.4.581] -12Wall PD, Melzack R. Textbook of pain Churchill Livingstone ]. The International Association for the Study of Pain defines pain as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in such terms” [13Merskey H, Spear FG. The concept of pain. J Psychosom Res 1967; 11(1): 59-67.https://www.sciencedirect.com/ science/article/pii/ 0022399967900578 [http://dx.doi.org/10.1016/0022-3999(67)90057-8] [PMID: 6049032] ]. This definition highlights the importance of not only the sensory and emotional aspects but also the potential for pain, suggesting cognitive processes associated with previous or future tissue damage. Thus, this definition presents pain not as a unimodal experience, but as a multifaceted phenomenon.
Multidimensionality of pain [10Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 1997; 277(5328): 968-71.http://www.ncbi.nlm.nih.gov/ pubmed/9252330 [http://dx.doi.org/10.1126/science.277.5328.968] [PMID: 9252330] ]. Pain is divided into sensory-discriminative, affective-motivational, and cognitive-evaluative components. Each provide a critical characteristic to the perception of pain.
The importance of pain and its quality as a homeostatic emotion can be further explained through drive-reduction theory (Fig. 2) [31Hull CL. Principles of behavior: An introduction to behavior theory. New York 1943.]. Pain creates an imbalanced state and an unpleasant affect needing to be resolved. This, in turn, motivates an organism to maintain internal stability by reacting in favor of survival. In other words, the affective-motivational component of pain is directly associated with the homeostatic and adaptive nature of pain. When pain (i.e. drive) is experienced by the organism, it disrupts homeostasis (i.e. need) and creates an unpleasant state. As a result, pain demands attention and requires a response that drives the organism to resolve, maintain, or revert to homeostasis by means of either escape or avoidance of the painful situation [5Craig AD. A new view of pain as a homeostatic emotion 2003; 26: 303-7.http://www.sciencedirect.com. ezproxy.uta.edu/science/ article/pii/S0166223603001231, 16Leknes S, Tracey I. A common neurobiology for pain and pleasure. Nat Rev Neurosci 2008; 9(4): 314-20.http://www.nature.com /articles/ nrn2333 [http://dx.doi.org/10.1038/nrn2333] [PMID: 18354400] , 31Hull CL. Principles of behavior: An introduction to behavior theory. New York 1943.-35Salcido CA, Harris Bozer AL, McNabb CT, Fuchs PN. Assessing the aversive nature of pain with an operant approach/avoidance paradigm. Physiol Behav 2018; 189: 59-63.https://www.sciencedirect.com/science/article/abs/pii/S0031938418301148 [http://dx.doi.org/10.1016/j.physbeh.2018.02.053] [PMID: 29501556] ]. Therefore, we propose that pain drives homeostatic behavior through emotional/motivational processes and cognitive processes, including elements associated with decision-making.
Decision-making is regarded as the cognitive process that involves identifying and assessing possible alternatives in order to solve a problem or achieve some objective [36Schall JD. Decision making. Curr Biol 2005; 15(1): R9-R11.https://www-sciencedirect-com.ezproxy.uta.edu/science/ article/pii/ S0960982204009728 [http://dx.doi.org/10.1016/j.cub.2004.12.009] [PMID: 15649356] ]. Good decision-making processing is especially advantageous and is critical for survival. Under normal circumstances, decision-making involves evaluating an almost unlimited number of alternatives to a current situation to assess the best outcome of long-term behavioral consequences [37Damasio AR, Tranel D, Damasio HC. Somatic markers and the guidance of behavior: Theory and preliminary testing. Frontal Lobe Function and Dysfunction 1991; 217-9.-39Muñoz JM. Somatic markers, rhetoric, and post-truth. Front Psychol 2017; 8: 1273.http://www.ncbi.nlm.nih.gov/pubmed/28798708 [http://dx.doi.org/10.3389/fpsyg.2017.01273] [PMID: 28798708] ]. When decisions are suitable, cognition ensures that the ratio of benefits, costs, and consequences are favorable to current needs and optimizing utility at small costs [40Goldstein I. Why people prefer pleasure to pain. Philosophy 1980; 55(213): 349-62.http://www.journals.cambridge.org/abstract _S0031819100049251 [http://dx.doi.org/10.1017/S0031819100049251] -42Higgins ET. Beyond pleasure and pain: How motivation works. Beyond pleasure and pain: How motivation works. 2012; 1-576.]. Information regarding homeostatic status, sensory input, and prediction of future threats or benefits are required for decision processes. This is essential in ensuring the maximum number of ongoing, and possibly competing for homeostatic needs are met. Emotional or somatic processes also aid in guiding behavior and decisions. This occurs in a biased manner even in situations where there are no definitive right or wrong answers and instead cause intuitions that lead to a more perceived correct choice [43Anderson SW, Bechara A, Damasio H, Tranel D, Damasio AR. Impairment of social and moral behavior related to early damage in human prefrontal cortex. Nat Neurosci 1999; 2(11): 1032-7. [http://dx.doi.org/10.1038/14833] [PMID: 10526345] -45Koenigs M, Grafman J. The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex. Behav Brain Res 2009; 201(2): 239-43.http://www.ncbi.nlm.nih.gov/pubmed/19428640 [http://dx.doi.org/10.1016/j.bbr.2009.03.004] [PMID: 19428640] ]. Therefore, like pain, decision-making is also influenced by cognitive and emotional processes along with homeostatic information. Such overlap strongly suggests a strong association among homeostasis, pain, and decision-making processing (Fig. 3).
Dimensions of decision-making. Decisions are influenced by cognition, emotions, and homeostatic information to assess the best ratio of benefits to costs.
Since decision-making and pain have the common goal to engage behavior to maintain homeostasis, and imbalances of homeostasis impact decision-making and pain processes, various cortical and subcortical areas that subserve basic needs, somatic and autonomic responses, and behavioral expressions must be involved [50Levine DS. Brain pathways for cognitive-emotional decision making in the human animal. Neural Netw 2009; 22(3): 286-93. [http://dx.doi.org/10.1016/j.neunet.2009.03.003] [PMID: 19362803] , 65Ruff CC, Fehr E. The neurobiology of rewards and values in social decision making. Nat Rev Neurosci 2014; 15(8): 549-62. [http://dx.doi.org/10.1038/nrn3776] [PMID: 24986556] , 66Pessiglione M, Delgado MR. The good, the bad and the brain: Neural correlates of appetitive and aversive values underlying decision making. Vol. 5. Curr Opin Behav Sci 2015; 78-84. [http://dx.doi.org/10.1016/j.cobeha.2015.08.006] ]. For example, the hypothalamus and autonomic brainstem nuclei (basal forebrain, ventral striatum, Periaqueductal Gray (PAG), and other brain-stem nuclei) are responsible for generating the corresponding somatic responses from stimuli in the presence of a decision [67Gold JI, Shadlen MN. The neural basis of decision making. Annu Rev Neurosci 2007; 30(1): 535-74.http://www.annualreviews.org/ doi/10.1146/annurev.neuro.29.051605.113038 [http://dx.doi.org/10.1146/annurev.neuro.29.051605.113038] [PMID: 17600525] ]. The amygdala provides the negative or positive valence of the stimuli, promotes exploration, and demands attention towards a particular stimulus. Since the amygdala encodes the somatic valence or importance of the stimuli, it also serves as a convergence-divergence zone where the stimulus (primary inducer) or thought of the stimulus (secondary inducer) is coupled with a response [68Bechara A, Damasio H, Tranel D, Damasio AR. The iowa gambling task and the somatic marker hypothesis: Some questions and answers. Trends Cogn Sci (Regul Ed) 2005; 9(4): 159-62. [http://dx.doi.org/10.1016/j.tics.2005.02.002] [PMID: 15808493] , 69Damasio AR, Everitt BJ, Bishop D. The somatic marker hypothesis and the possible functions of the prefrontal cortex [and discussion]. Philos Trans R Soc B Biol Sci 1996.]. This processing is important to help guide future decisions since previous associations and outcomes play a major role in directing future decisions.
Table 1 Common neural correlates of pain and decision-making.
Additional areas of the prefrontal cortex, including the anterior cingulate, ventromedial prefrontal, lateral and dorsolateral prefrontal, and orbitofrontal cortex are also responsible for higher processing in regards to decision-making [69Damasio AR, Everitt BJ, Bishop D. The somatic marker hypothesis and the possible functions of the prefrontal cortex [and discussion]. Philos Trans R Soc B Biol Sci 1996.]. As a whole, the prefrontal cortex is proposed to be responsible for executive functions of cognition, especially regarding making decisions and controlling attention [70Fuster JM, Fuster JM. Chapter 8 – Overview of prefrontal functions: The temporal organization of action. In: The prefrontal cortex. 2008., 71Wallis JD. Orbitofrontal cortex and its contribution to decision-making. Annu Rev Neurosci 2007; 30(1): 31-56. [http://dx.doi.org/10.1146/annurev.neuro.30.051606.094334] [PMID: 17417936] ]. Within the prefrontal cortex, the anterior cingulate cortex is critical for detecting an error, conflict, or task difficulty. The anterior cingulate cortex is also involved in calculating benefits and costs associated with stimuli outcomes [20Fuchs PN, Peng YB, Boyette-Davis JA, Uhelski ML. The anterior cingulate cortex and pain processing. Front Integr Neurosci 2014; 8(35)http://www.ncbi.nlm.nih.gov/ pubmed/24829554 [http://dx.doi.org/10.3389/fnint.2014.00035] , 62Bush G, Vogt BA, Holmes J, et al. Dorsal anterior cingulate cortex: A role in reward-based decision making. Proc Natl Acad Sci USA 2002; 99(1): 523-8.http://www.ncbi.nlm.nih.gov/pubmed/11756669 [http://dx.doi.org/10.1073/pnas.012470999] [PMID: 11756669] , 72Webb CA, Weber M, Mundy EA, Killgore WDS. Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: A voxel-based morphometric analysis. Psychol Med 2014; 44(13): 2833-43.http://www.journals. cambridge.org/abstract_S0033291714000348 [http://dx.doi.org/10.1017/S0033291714000348] [PMID: 25066703] ] and has been shown to play a role in processing the affective/motivational dimension of pain [21McNabb CT, Uhelski ML, Fuchs PN. A direct comparison of affective pain processing underlying two traditional pain modalities in rodents. Neurosci Lett 2012; 507(1): 57-61. [http://dx.doi.org/10.1016/j.neulet.2011.11.051] [PMID: 22172927] , 33LaBuda CJ, Fuchs PN. A behavioral test paradigm to measure the aversive quality of inflammatory and neuropathic pain in rats. Exp Neurol 2000; 163(2): 490-. [http://dx.doi.org/10.1006/exnr.2000.7395] , 62Bush G, Vogt BA, Holmes J, et al. Dorsal anterior cingulate cortex: A role in reward-based decision making. Proc Natl Acad Sci USA 2002; 99(1): 523-8.http://www.ncbi.nlm.nih.gov/pubmed/11756669 [http://dx.doi.org/10.1073/pnas.012470999] [PMID: 11756669] , 73Fuchs PN, McNabb CT. The place escape/avoidance paradigm: A novel method to assess nociceptive processing. J Integr Neurosci 2012; 11(1): 61-72. [http://dx.doi.org/10.1142/S0219635212500045] [PMID: 22744783] ]. Thus, the anterior cingulate cortex plays a critical role in pain affect and evaluating our decisions by assessing multiple factors.
The ventromedial prefrontal cortex also plays a role in decision-making [74Bechara A, Damasio H, Damasio AR, Lee GP. Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making. J Neurosci 1999; 19(13): 5473-81. [http://dx.doi.org/10.1523/JNEUROSCI.19-13-05473.1999] [PMID: 10377356] , 75Bechara A, Tranel D, Damasio H. Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions. Brain 2000; 123(Pt 11): 2189-202.https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/123.11.2189 [http://dx.doi.org/10.1093/brain/123.11.2189] [PMID: 11050020] ] and is involved in the integration of emotion and cognition. The ventromedial prefrontal cortex is responsible for the “gut feeling” potentiated by the emotion of a good or bad decision in presence of a moral dilemma [43Anderson SW, Bechara A, Damasio H, Tranel D, Damasio AR. Impairment of social and moral behavior related to early damage in human prefrontal cortex. Nat Neurosci 1999; 2(11): 1032-7. [http://dx.doi.org/10.1038/14833] [PMID: 10526345] , 44Blair RJR. The amygdala and ventromedial prefrontal cortex in morality and psychopathy. Trends Cogn Sci (Regul Ed) 2007; 11(9): 387-92. [http://dx.doi.org/10.1016/j.tics.2007.07.003] [PMID: 17707682] , 76Koenigs M, Young L, Adolphs R, et al. Damage to the prefrontal cortex increases utilitarian moral judgements. Nature 2007; 446(7138): 908-11. [http://dx.doi.org/10.1038/nature05631] [PMID: 17377536] ]. Regardless if there are no correct answers on moral tasks, emotions ultimately provide a decision that feels more correct. Though this heuristic can enhance decisions, emotions can also reduce the efficacy of rational decisions.
The lateral prefrontal cortex is critical for executive control and, along with the anterior cingulate cortex and the parietal cortex, is partly responsible for control of attention [70Fuster JM, Fuster JM. Chapter 8 – Overview of prefrontal functions: The temporal organization of action. In: The prefrontal cortex. 2008.]. Although the lateral prefrontal cortex and especially the dorsolateral prefrontal cortex is thought to be primarily involved in purely cognitive functioning, recent studies have revealed evidence for the integration of cognition and emotion in this area [77Barbey AK, Koenigs M, Grafman J. Dorsolateral prefrontal contributions to human working memory. Cortex 2013; 49(5): 1195-205. [http://dx.doi.org/10.1016/j.cortex.2012.05.022] [PMID: 22789779] , 78Fellows LK, Farah MJ. Different underlying impairments in decision-making following ventromedial and dorsolateral frontal lobe damage in humans. Cereb Cortex 2005; 15(1): 58-63. [http://dx.doi.org/10.1093/cercor/bhh108] [PMID: 15217900] ]. In fact, emotional valence photos could modulate activity in these areas where pleasant photos increased activity and unpleasant photos decreased activity compared to control photos [79Perlstein WM, Elbert T, Stenger VA. Dissociation in human prefrontal cortex of affective influences on working memory-related activity. Proc Natl Acad Sci USA 2002; 99(3): 1736-41. [http://dx.doi.org/10.1073/pnas.241650598] [PMID: 11818573] ].
The orbitofrontal cortex, like the amygdala, can discriminate positive and negative values of stimuli by integrating sensory and affective information. This stimulus evaluation provided by the amygdala and the orbitofrontal cortex appears to also be responsible for action strategies for current and also future anticipatory occurrences [53Hooker CI, Knight RT. The role of lateral orbitofrontal cortex in the inhibitory control of emotion.2010., 80Naqvi N, Tranel D, Bechara A. Visceral and decision-making functions of the ventromedial prefrontal cortex.2010.-82O’Doherty J. Can’t learn without you: predictive value coding in orbitofrontal cortex requires the basolateral amygdala. Neuron 2003; 39(5): 731-3. [http://dx.doi.org/10.1016/S0896-6273(03)00525-7] [PMID: 12948440] ]. As a result, both regions refer to critical associations with previous decisions and consequences such that current decisions will be better suited to the wanted outcome.
Homeostasis, pain, and cognition can individually impact behavior through powerful biological mechanisms. However, these systems do not act in isolation. Indeed, there is considerable conceptual and neurobiological overlap that highlights the close interaction of decision-making, pain, and homeostasis. Reductively, this relationship is founded upon pain requiring and eliciting a decision. Certainly, when pain is presented, an organism must ultimately choose whether to escape/avoid or approach/allow it. Yet this interplay becomes more profound when the rationale for similarity is extended further to include the shared characteristics of homeostasis and emotional and cognitive qualities. Ultimately then, the decision to either escape or allow pain entirely depends on the current homeostatic information which includes current affective, attentional, motivational influences. Under this idea, it is no wonder that pain is a multidimensional phenomenon that directly impacts homeostasis through its three modalities. To summarize entirely, the sensory component of pain allows an organism to be aware of where and how the homeostatic disturbance occurs, while the affective-motivational component demands attention and motivates an organism to resolve the pain, and the cognitive-evaluative component provides the organism with a solution- a behavioral choice based on previous and current pain situations and what outcomes that are associated with those choices. Thus, pain disturbs the ideal state homeostasis requires and as a result, drives a decision. This positive feedback loop is necessary for survival.
Even more, under this same notion, decision-making is considered the aiding force of homeostasis. Decisions utilize homeostatic information to cognitively and emotionally assess which alternatives provide a more ideal state determined by cost versus benefit. As a result, decisions promote homeostasis and aid in reverting to the ideal state. Pain, in this case, is a stressor and changes the ideal state, whereas the decision to escape or avoid pain returns homeostatic equilibrium. Additionally, because homeostasis can be reduced to a mechanism of maintenance, resistance, and survival, pain and decision-making are necessary for completing that loop [1Cannon WB. Organization for physiological homeostasis. Physiol Rev 1929; 9(3): 399-431. [http://dx.doi.org/10.1152/physrev.1922.214.171.1249] , 5Craig AD. A new view of pain as a homeostatic emotion 2003; 26: 303-7.http://www.sciencedirect.com. ezproxy.uta.edu/science/ article/pii/S0166223603001231, 32Fields HL. A motivation-decision model of pain: The role of opioids. Proceedings of the 11th world congress on pain 2006; 449-59., 83Bechara A. Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective. Nat Neurosci 2005; 8(11): 1458-63. [http://dx.doi.org/10.1038/nn1584] [PMID: 16251988] ]. This then could suggest that these entities may not be truly separate systems, but rather interconnected.
Evolutionarily, this concept makes sense. By design, each of these biological mechanisms plays a role in increasing the odds of survival. Functionally, it is anatomically and behaviorally efficient to combine similar like mechanisms along parallel, if not overlapping biological pathways especially when each component revolves around a central goal of survival. Thus, the link between homeostasis, pain, and cognition can be further expounded through the perspective of survival through three means: an alerting system through pain, a mechanism of checks and balances provided by homeostasis, and requirement of action driven by decision-making.
The undeniable overlap in both neural signatures and a conceptual understanding of these phenomenon suggests the importance of survival. However, the numerous factors that can individually influence pain, decisions, and homeostasis, may also play a role in modulating survival. Thus, it may be imperative to consider this complex and integrated relationship when attempting to understand the multi-dimensionality of pain and may provide further insight into how pain and pain treatments may differ across individuals.
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