Pain and Immune System Biopsychology Lecture Notes PDF

Pain Biopsychology M.Sc. Marla Joy Mierzejewski Semester schedule 1 Introduction + Central nervous system 28.10.2024 2 Peripheral nervous system + Neurons 04.11.2024 3 Drugs + Psychiatric disorders + Sensory system 1...

Pain Biopsychology M.Sc. Marla Joy Mierzejewski Semester schedule 1 Introduction + Central nervous system 28.10.2024 2 Peripheral nervous system + Neurons 04.11.2024 3 Drugs + Psychiatric disorders + Sensory system 1 11.11.2024 4 Sensory system 2 + Movement + Pain 1 18.11.2024 5 Pain 2 + Immune system + Stress 25.11.2024 6 Heart + Breath + Hunger 02.12.2024 7 Sleep + Sexuality + Genetics 09.12.2024 8 Methods + Recap 16.12.2024 University of Europe for Applied Sciences Recap 5 sensory systems  Visual, auditory, olfactory, gustatory, haptic system  Homunculus Motor system:  Basal ganglia, cerebellum, thalamus, brain stem, spinal cord  Neuroplasticity  Biofeedback Pain  Acute vs. chronic pain  Pain diagnostic University of Europe for Applied Sciences  Research Research in groups of 4 - 5 until next week: How does the pain sensation and processing work? What are „nociceptors“ and what is their task? Which brain areas are essential for pain processing? Present your findings (approx. 10 min.) University of Europe for Applied Sciences Pain conduction Nociceptors Perception of thermal, chemical or mechanical stimuli that potentially or actually harm the body Almost everywhere in the body Nociceptor is NOT a pain receptor! Procedure  Nociceptor: receives stimuli –> signal to spinal cord -> Thalamus  Thalamus: filters important information -> lateral & medial system & frontal cortex  Lateral system: signal reaches somatosensory cortex (conscious perception of pain)  Medial system: signal reaches limbic system (affective component of pain, subjective meaning)  Frontal cortical areas: memory, experience University of Europe for Applied Sciences https://injurycenter.umich.edu/opioid-overdose/michigan-safer-opioid-prescribing-toolkit/background-on-opioid-use-pain-and-pain- management/definition-types-of-pain/patients/ University of Europe for Applied Sciences Chronic pain Risk factors Current stressors, e.g. stress at work, family conflicts Operant reinforcement: leads to more pain behaviour and also to stronger pain Operant mechanisms: regarding medication intake and activity design Model learning Attention processes Iatrogenic influences  Over-diagnostics  Incorrect information (long rest, prescription of bed rest)  Incorrect medication (inappropriate or several similar pain medications before looking for alternatives) University of Europe for Applied Sciences Chronic pain Risk factors First learning processes on the level of the posterior horn Cerebral changes in the form of expanded representations in the somatosensory cortex  Somatosensory „pain memory“ https://glacierviewlodge.ca/memory-album/ University of Europe for Applied Sciences Pain sensitivity Periphere sensitivity  Substances released from damaged tissue sensitize the nociceptors or activate “sleeping" nociceptors  very slight stimuli can trigger pain  Damaged tissue is more sensitive and more susceptible to pain than healthy tissue  In addition, damaged or activated nociceptive fibers form neuropeptides, which have a pro-inflammatory effect and also lead to a sensitization of the tissue Central sensitivity  Synaptic changes: e.g. due to increased release of glutamate (pain-mediating transmitter) in the spinal cord or brain by tissue injury  Altered excitability of nociceptive neurons: e.g. prolonged, inadequately treated pain may result in altered membrane properties and thus increased excitability of postsynaptic nociceptive neurons  Pain sensitivity through biological plasticity & “pain memory” University of Europe for Applied Sciences Pain perception Why do people perceive pain differently? Perception threshold  Intensity level of a physical stimulus at which the stimulus is consciously perceived Tolerance threshold  Intensity strength of a pain stimulus up to which the pain is bearable E.g.: Ice water experiment on pain tolerance for more information: McIntyre et al. (2020), Von Baeyer et al. (2005) Subjects with high self-efficacy expectations tolerated ice water longer University of Europe for Applied Sciences  Brainstorming Do you know a person who constantly suffers from pain? Where does the pain come from? How does this person behave? University of Europe for Applied Sciences Chronic pain Definition Stage 1 Stage 2 Stage 3 Temporal Intermittent Continuous Continuous Limited in time Changing intensity Intensity hardly changing Spatial/ Paraphrased Extended to neighboring Extended to other areas, localization areas changing places Behavior Adequate medication Partly abuse of medicines Medication misuse frequent Doctor consultation Change of doctor Doctor hopping Hospital/Surgery (1x) Hospital/Surgery (2-3x) Hospital/Surgery (> 3x) "Sick role" "Disability role" “Learned helplessness" University of Europe for Applied Sciences Pain disorder in ICD-10 F45.4 Persistent pain disorder At least 6 months of continuous, severe and distressing pain in a body part that is not adequately explained by the evidence of a physiological process or physical disorder, and which is persistently the primary focus of the patient Not during schizophrenia or exclusively during affective, (undifferentiated) somatization disorder, or hypochondria disorder F45.40 persistent somatoform pain disorder F45.41 chronic pain disorder with somatic and psychological factors University of Europe for Applied Sciences  Pain disorder in ICD-11 General symptoms, signs or clinical findings MG30.00 chronic primary visceral pain MG30 chronic pain: Pain is an unpleasant sensory and MG30.01 chronic primary widespread pain emotional experience associated with, or resembling that associated with, actual or potential tissue damage. Chronic MG30.02 chronic primary musculoskeletal pain pain is pain that persists or recurs for longer than 3 months. MG30.03 chronic primary headache or orofacial pain Chronic pain is multifactorial: biological, psychological and social factors contribute to the pain syndrome. MG30.1 chronic cancer related pain MG30.2 chronic postsurgical or post traumatic pain MG30.0 chronic primary pain: Chronic primary pain is MG30.3 chronic secondary musculoskeletal pain chronic pain in one or more anatomical regions that is characterised by significant emotional distress (anxiety, MG30.4 chronic secondary visceral pain anger/frustration or depressed mood) or functional MG30.5 chronic neuropathic pain disability (interference in daily life activities and reduced participation in social roles). Chronic primary pain is MG30.6 chronic secondary headache or orofacial pain multifactorial: biological, psychological and social factors contribute to the pain syndrome. The diagnosis is appropriate independently of identified biological or https://icd.who.int/browse11/l-m/en psychological contributors unless another diagnosis would better account for the presenting symptoms. University of Europe for Applied Sciences  Videos Two videos about pain: https://www.youtube.com/watch?v=ikUzvSph7Z4 https://www.youtube.com/watch?v=lVdulzi6oYw University of Europe for Applied Sciences Phantom Pain Definition Pain that occurs in an amputated part of the body  Tingling  Touch sensations  Cold and heat thrusts Mainly due to changes in the nervous system of the brain  Functional reorganization of the somatosensory cortex - e.g. neurons of the missing arm respond to signals from nearby neurons (e.g. face) and get stimulated, even though the arm is not there anymore  Internal representation of the body: representation remains intact after loss of limb (e.g. eyes see no leg but brain expects a leg to be there)  PNS: damaged axons form a neuroma – generate action potentials University of Europe for Applied Sciences  Video Phantom limb: https://www.youtube.com/watch?v=GYxksqaLBxc University of Europe for Applied Sciences Pain therapy University of Europe for Applied Sciences  Research Create 6 groups. Each topic will be represented twice. Answer the following question: How can this type of pain be treated?  Group 1: Acute pain  Group 2: Chronic pain  Group 3: Phantom pain Gather treatment options and illustrations for them. Present your results (approx. 5 – 10 min). University of Europe for Applied Sciences Pain therapy Overview Acute pain Phantom pain  Medication  Tablets, pain pump  Prosthesis (perceived as fused)  Appropiate activity  Mirror therapy  Physiotherapy Chronic pain  EMG Biofeedback  Physiotherapy  Relaxation method  Cognitive behavioral therapy  Imagination EMG biofeedback (Tölle & Flor, 2006)  Mindfulness  Pain/stress management strategies University of Europe for Applied Sciences Immune system Biopsychology M.Sc. Marla Joy Mierzejewski  Brainstorming What do we have an immune system for? What belongs to the immune system? What does it influence? What if it‘s not functioning properly? University of Europe for Applied Sciences  Reading Please read the text ”05_The innate and adaptive immune systems“ and answer the following questions:  What is the role of innate immune defense?  What is the role of the acquired immune defense?  How does an immune reaction work? Then discuss your findings with your neighbour. University of Europe for Applied Sciences Immune system Structure Protective function  Differentiate between „good“ and „bad“ cells – must recognize „opponent“, e.g. bacteria, viruses, fungi  Adequate defense through antigens – protein molecules at the surface of a cell („marks“ cell as good or bad) Innate immune system  Unspecific barriers are fast and act against most „enemies“  External barriers (skin, mucous membranes, stomach acid, urine)  Phagocyte, macrophages, natural killer cells: specialized body cells for destroying  Dendritic cells: connection between innate and specific system Adaptive immune system  Specific barriers against specific kinds of „enemies“ – lymphocytes (= Leucocytes/ white blood cells)  Cell-mediated immunity: T-lymphocytes  Antibody-mediated immunity: B-lymphocytes University of Europe for Applied Sciences Immune system T & B cells Cell-mediated immune defense – T-Lymphocytes  Macrophage (=phagocyte) ingests a foreign micro organism  Presents the antigen of the micro organism on its cell membrane surface (attracts T-cells)  T-cells binds to a receptor of the infected macrophage -> T-cells multiply -> destroy infected body cell Antibody-mediated immune defense – B-Lymphocytes  B-cell binds to a foreign antigen -> B-cell multiplies -> synthesizes a deadly receptor molecule „antibody“  Antibody binds in intracellular space to antigen and destroys it B- and T-memory cells are developed for future infections with same organism Both processes last several days for the first time – then faster because of memory cells University of Europe for Applied Sciences  Video Innate and adaptive immune system: https://www.youtube.com/watch?v=PzunOgYHeyg University of Europe for Applied Sciences Immune system and vaccination University of Europe for Applied Sciences Immune system Principle of vaccination Injection of killed or attenuated pathogens Reaction of the body with the formation of antibodies and memory cells Activation on contact with real pathogen (immune) University of Europe for Applied Sciences Immune system Infection vs. vaccination - Covid 19 https://www.immunology.org/public-information/vaccine-resources/covid-19/covid- 19-vaccine-infographics/covid-immunity-infection-vaccine University of Europe for Applied Sciences Immune system Infection vs. vaccination - measles High infectivity rate - threshold for community protection at least 95% immunity to prevent epidemics Consequences of outbreaks: suffering during infection, costs for health care system, deaths in those countries with gaps in their immunization programmes  E.g.: Democratic Republic of the Congo: 2.299 people died during the Ebola epidemic vs. 7.800 deaths from measles, both in same time period of 2018–2020 Risk of infection vs. risk of vaccination? https://www.unicef.org/eca/stories/how-dangerous-measles University of Europe for Applied Sciences  Research Please research on your own regarding the following topic (approx. 10 min.): The correlation between measles vaccination and autism in the US Ideally, you find some research papers regarding this topic. University of Europe for Applied Sciences Immune system Infection vs. vaccination - measles Myth about correlation between measles vaccination and autism in the US  The myth of a link between vaccination and autism arose from a 1998 case report study by British physician Andrew Wakefield  Wakefield had to withdraw the study because of weaknesses (N = 12, most of the co-authors distanced themselves from the conclusions) and studies could not replicate his findings  But: fear still persists and is often cited by vaccination sceptics  Latest study by Hviid A. et al. (2019) – no link between autism and measles vaccination University of Europe for Applied Sciences  Video Development of vaccination: https://www.youtube.com/watch?v=m0yu4y-y7kI&list=PLooF83S- sY9BXClESLUpIEq_X7mGP9MaJ&index=12 University of Europe for Applied Sciences Disorders of the immune system Possible causes Born with a weak immune system “primary immune deficiency” Get a disease or take medicine that weakens the immune system “acquired immune deficiency” Overactive immune system - can cause e.g. allergic rhinitis, asthma, eczema Immune system turns against own body cells “autoimmune disease”  Type 1 diabetes: immune system attacks cells in the pancreas that produce insulin  Rheumatoid arthritis: swelling and deformation of joints University of Europe for Applied Sciences Stress Biopsychology M.Sc. Marla Joy Mierzejewski Brainstorming Please take a few minutes to think about the following question: How can you tell that you are stressed? Then discuss your ideas with your neighbor. University of Europe for Applied Sciences Stress Definition Biological concepts Psychological concepts Fight or flight Critical life events (Cannon, 1932) (Holmes & Rahe, 1964) General Transactional stress theory Adaptation Syndrome (Lazarus, 1974) (AAS, Selye, 1936) Theory of resource conservation Allostatic Load (Hobfoll, 1989) (McEwen, 1998) Reaction-oriented Stimulus-oriented University of Europe for Applied Sciences Stress Definition Body reacts to damage or threat with several physiological changes = stress reaction Stressors – Psychological: sad about job loss – Physical: long exposure to cold  associated with higher levels of glucocorticoids, adrenalin, norepinephrine Two sides of stress reaction – Short-term: adaptive (mobilizes energy, immune defense) – Long-term: changes that damage body (e.g. enlarged adrenal glands) Intensity of stress reaction depends on the individual and its coping mechanisms University of Europe for Applied Sciences Stress Three components Stressor Stress response (Threatening environmental Detect threat (Activation of physiological stimulus) systems) Events and experiences Unconsciously or Sympathetic nervous system that indicate an actual or consciously (emergency response) potential change in Hypothalamic-pituitary- homeostasis (e.g., adrenal axis 'mismatch' between reality and expectation) University of Europe for Applied Sciences Stress Location in the brain Adrenal axis Glucocorticoids (e.g. cortisol): most frequently used physiological measure for stress University of Europe for Applied Sciences Stress Fight and flight - an acute emergency response https://en.wikipedia.org/wiki/Fight-or-flight_response https://www.brigitte.de/aktuell/stimmen/sicherheit--sicher-ist--selbst- sicher--unsere-angst-im-dunkeln-10173874.html https://www.verywellmind.com/what-is-the-fight-or-flight-response-2795194 University of Europe for Applied Sciences Stress Fight and flight - an acute emergency response What? Preparation of the organism for fight or flight through the redistribution of resources http://medicalstate.tumblr.com/post/1409335505/homeostasis-the-two-people-you-should-know When? In case of existing acute stressors/acute threat How? Activation of the sympathetic and deactivation of the parasympathetic nervous system Increased release of adrenalin from the adrenal medulla Effect: higher performance But: slower wound healing after operation Walter Cannon (1871-1945) Physiologist University of Europe for Applied Sciences Recap Sympathetic and parasympathetic nervous system Sympathetic nervous system  Activation and performance  E.g. Fight and Flight Parasympathetic  Counterpart of the sympathetic nervous system  Body functions and relaxation  Rest and digest University of Europe for Applied Sciences Stress Trier Social Stress Test Paradigm for provoking a natural stress response  Interview and calculation task  Central aspect: psychosocial stressors (e.g. lack of feedback) Impact  Increases in heart rate  Increase blood pressure https://www.eurekalert.org/multimedia/669620  Release of some endocrine stress markers, e.g., cortisol, alpha-amylase for more information: e.g. Allen et al. (2016) University of Europe for Applied Sciences Research Please divide into groups of 4-5 and research: What is the HPA axis (Hypothalamic-pituitary-adrenocortical axis)? Which functions do the hormones CRH, ACTH and cortisol have? Then discuss your findings in plenary! University of Europe for Applied Sciences  Video The HPA axis: https://www.youtube.com/watch?v=QAeBKRaNri0 University of Europe for Applied Sciences Stress Hypothalamic-pituitary-adrenocortical axis After exposure to a stressor Hormone cascade  Corticotropin releasing hormone (CRH) from hypothalamus  Adrenocorticotropic hormone (ACTH) from pituitary gland  Cortisol from adrenal cortex Effect on metabolism (among others)  Activation...... of glycogen degradation... the formation of glucose  Inhibition...... of the immune functions... inflammatory processes https://empoweredhealthinsti tute.com/what-is-the-hpa- University of Europe for Applied Sciences axis/ Stress Hypothalamic-pituitary-adrenocortical axis Corticotropin releasing hormone (CRH) from hypothalamus  Central driver of the stress hormone system  Suppresses appetite, increases anxiety, improves memory and selective attention – fine tuning of body‘s reaction in stressful experience  E.g. released during pregnancy by fetus and placenta – increased cortisol – starts labor  Causes release of adrenocorticotropin due to stimulation of pituitary gland Adrenocorticotropic hormone (ACTH) from pituitary gland  High in the morning, lowest during sleep  Increases production of chemical compounds that trigger other hormones like adrenalin/noradrenalin  When it reaches adrenal glands, it causes secretion of cortisol – higher level in the blood Cortisol from adrenal cortex  When released, the release of CRH and ACTH slows down and cortisol level falls – negative feedback loop University of Europe for Applied Sciences Stress Normal reaction process Physiological response Activity recreation Time McEwen (2000) University of Europe for Applied Sciences Stress Allostasis and allostatic load Allostasis  "Stability through change“ – restore homeostasis during a challenge  Physiological and hormonal adaptation reactions to acute stress  Beneficial adaptation in case of short-term activation (e.g. immune system, hazard-relevant memory formation) Allostatic load  Cost of adaptation to stress over time  Presence of too much stress or inefficient operation of the hormone response system  Harmful changes with long-term activation (e.g. immune suppression) University of Europe for Applied Sciences Stress Allostasis and allostatic load Chronic stress: harmful reaction to the accumulation of allostatic loads lack of adaptation physiological reaction Normal adaptation McEwen (2000). Time University of Europe for Applied Sciences Stress Oxytocin as an antagonist "Cuddle/bonding hormone“ (e.g. responsible for caring behavior, milk flow) Distribution on contact Counterpart, i.e. stress-reducing hormone Effects  Strengthening the couple bond  Building trust in other people  Reduction of stress and anxiety  Damping aggression  Empathy University of Europe for Applied Sciences Stress Physical touch as an antagonist? Ditzen et al. (2007) University of Europe for Applied Sciences  Brainstorming Form groups of 4-5 and discuss the following question: When, how and why does stress play a role in the development of diseases? University of Europe for Applied Sciences Immune system & stress Effect of stress on the immune system  Short-term: