Anatomy and physiology of pain Clinically, pain can be labeled nociceptive if it is inferred that the pain is due to ongoing activation of the nociceptive system by tissue injury. Nociceptive Pain Although neuroplastic changes (such as those underlying tissue sensitization) are clearly involved, nociceptive pain is presumed to occur as a result of the normal activation of the sensory system by noxious stimuli, a process that involves 4 basic processes transduction transmission perception of pain modulation of pain Nociceptive Pain Tissue injury activates primary afferent neurons called nociceptors, which are small diameter afferent neurons (with A-delta and C-fibers) Nociceptors Nociceptors respond to noxious stimuli Nociceptors are found in skin muscle joints and some visceral tissues. Nociceptors Nociceptive primary afferent neurons are varied: most are silent (may not respond to standard stimuli, only than inflammatory substances are present) some are specific to one type of stimulus, such as - mechanical - or thermal but most are polymodal (respond to many stimuli) the number and size of the receptive fields served by each fiber may be small or large, respectively Nociceptors nociceptors free nerve endings has capacity to distinguish between noxious and innocuous stimuli when exposed to mechanical (incision or tumor growth) thermal (burn, ice) chemical (toxic substance) stimuli tissue damage occurs substances are released by the damaged tissue which facilitates the movement of pain impulse to the spinal cord Nociceptors The substances released from the affected tissue are: prostaglandins bradykinin serotonin substance P histamine protons NGF The role of this substances provide opportunities for the development of new analgesic drugs Substances released Non-steroidal anti-inflammatories, such as ibuprofen, are effective in minimizing pain because they minimize the effects of these substances released, especially prostaglandins. Corticosteroids, such as dexamethasone used for cancer pain, also interferes with the production of prostaglandins. Clinical significance sufficient amounts of noxious stimulation cause the cell membrane of the neuron (nervous system cell) to become permeable to sodium ions, allowing the ions to rush into the cell and creating a temporary positive charge. then potassium transfers back into the cell, thus changing the charge back to a negative one. with this depolarization and repolarization, the noxious stimuli is converted to an impulse this impulse takes just milliseconds to occur. Transduction Clinical significance Some analgesics relieve pain primarily by decreasing the sodium and potassium transfers at the neuron level, thereby slowing or stopping pain transmission. Examples: - local anesthetics, - anticonvulsants used for neuropathic pain, migraines. once depolarization occurs, transmission of information proceeds proximally along the axon to the spinal cord and then on to higher centers. Transmission transmission across the first central synapse may be influenced by activity in the primary afferent itself and modulatory neural pathways. that originate segmentally or supraspinally. further modulation results from processes initated by glial cells. Transmission impulse spinal cord brain stem thalamus central structures of brain pain is processed. neurotransmitters are needed to continue the pain impulse from the spinal cord to the brain. Transmission Clinical significance the end result of the neural activity of pain transmission it is believed pain perception occurs in the cortical structures - behavioral strategies and therapy can be applied to reduce pain. brain can accommodate a limited number of signals - distraction, relaxation signals may get through the gate, leaving limited signals (such as pain) to be transmitted to the higher structures. Perception of pain The neurochemistry of these processes involves an extraordinary array of compounds, including - endorphins, - neurokinins, - prostaglandins, - biogenic amines, - GABA, - neurotensin, - cannabinoids, - purines, - and many others. Modulation of pain The endorphinergic pain modulatory pathways are characterized by multiple endogenous ligands and different types of opioid receptors: mu, delta, and kappa. Endorphins are present in the periphery, on nerve endings, immune-related cells, and other tissues, Endorphins are widely distributed in the central nervous system (CNS). They are involved in many neuroregulatory processes apart from pain control, including the stress response and motor control systems. Opioid drugs mimic the action of endogenous opioid ligands. Most of the drugs used for pain are full mu receptor agonists. Modulation of pain Other pain modulating systems, such as those that use - monoamines (serotonin, norepinephrine and dopamine), - histamine, - acetylcholine, - cannabinoids, - growth factors - and other compounds, are targets for nontraditional analgesics, such as specific - antidepressants and - anticonvulsants. It is likely that entirely novel analgesic compounds will become commercially available in the future as drug development programs target these systems. Modulation of pain changing or inhibiting pain impulses in the descending tract (brain spinal cord). descending fibers also release substances such as norepinephrine and serotonin (referred to as endogenous opioids or endorphins) which have the capability of inhibiting the transmission of noxious stimuli. cancer pain responds to antidepressants which interfere with the reuptake of serotonin and norepinephrine which increases their availability to inhibit noxious stimuli. Modulation of pain Pathophysiology of visceral pain Visceral pain: Types - angina pectoris, myocardial infarction, acute pancreatitis, cephalic pain, prostatic pain, nephro-lytiase pain. Receptors: unmyelinated C fibres For human pathophysiology the kinds of stimuli apt to induce pain in the viscera are important. It is well-known that the stimuli likely to induce cutaneous pain are not algogenic in the viscera. This explains why in the past the viscera were considered to be insensitive to pain. Pathophysiology of visceral pain Visceral pain stimuli: abnormal distention and contraction of the hollow viscera muscle walls rapid stretching of the capsule of such solid visceral organs as are the liver, spleen, pancreas. abrupt anoxemia of visceral muscles formation and accumulation noxious substances direct action of chemical stimuli (oesophagus, stomach), traction or compression of ligaments and vessels inflammatory processes necrosis of some structures (myocardium, pancreas) Pathophysiology of visceral pain Mechanisms involved in referred pain: convergence of impulses from viscera and from the skin in the CNS: - sensory impulses from the viscera create an irritable focus in the segment at which they enter the spinal cord. -afferent impulses from the skin entering the same segment are thereby facilitated, giving rise to true cutaneous pain. senzitization of neurons in dorsal horn Pathophysiology of visceral pain Painful visceral afferent impulses activate anterior horn motor cells to produce rigidity of the muscle (visceromotor reflexes) A similar activation of anterolateral autonomic cells induces pyloerection, vasoconstriction, and other sympathetic phenomena These mechanisms, which in modern terms can be defined as positive sympathetic and motor feedback loops, are fundamental in refered pain It is clear that painful stimulation of visceral structures evokes a visceromuscular reflex, so that some muscles contract and become a new source of pain Referred visceral pain Intricate conditions - in some types of pain, e.g. chest pain, is difficult to distinguish the true cause of pain because such kind of pain may be related to cervical osteoarthrosis, esophageal hernia, or cholecystitis. It is difficult to ascertain whether these intricate conditions are due to a simple addition of impulses from different sources in the CNS or to somatovisceral and viscerosomatic reflex mechanisms. Clinical aspects It has been demonstrated that the modulation process is facilitated if the experience to be retained is repeated many times or is accompanied by pleasant or unpleasant emotions. Pain is, at least in part, a learned experience - e.g. during the first renal colic, true parietal pain followed visceral pain after a variable interval. In subsequent episodes of renal colic pain, parietal pain developed promptly and was not preceded by true visceral pain. This is probably due to the activation of central modulation. Clinical aspects EVALUATION OF PAIN EXPERIMENTAL EVALUATION OF PAIN Somatic pain models Hot plate test Tail flick test Tail immersion test Analgezimeter test Visceral pain models Writhing testCapsaicin colon stimulation testInflammatory cystitis test (clyclophosphamide) Behavioural models Activity cage testHole board test Pletismometer test Inflammation models Subcutaneous pellets implantation !!! The results obtained in experiments can not be directly extrapolated in humans CLINICAL EVALUATION OF PAIN Description: severity, quality, location, temporal features, frequency, aggravating & alleviating factors Previous history Context: social, cultural, emotional, spiritual factors Meaning Interventions: what has been tried? Pain history Physical exam in pain assessment Inspection / Observation facial expression: grimacing; appears anxious; flat affect body position and spontaneous movement: there may be positioning to protect painful areas, limited movement due to pain diaphoresis can be caused by pain areas of redness, swelling atrophied muscles localized tenderness to pressure or percussion fullness / mass induration / warmth Physical exam in pain assessment Palpation Important in evaluating pain, due to the possibility of spinal cord compression, and nerve root or peripheral nerve lesions Sensory examination Areas of numbness / decreased sensation Areas of increased sensitivity, such as allodynia or hyperalgesia Motor (strength) exam Deep tendon reflexes intensity, symmetry Hyperreflexia and clonus: possible upper motor neuron lesion, such as spinal cord compression or cerebral metastases. Hyoporeflexia - possible lower motor neuron impairment. Physical exam in pain assessment neurological examination Use a numeric pain rating scale in most clinical settings. The most common is an 11 point scale where 0 = no pain and 10 =worst pain imaginable. Many use a 0 to 5 faces scale for children. Assessing pain intensity in children Assessing pain intensity Diagnosis Medical diagnoses related to the pain: underlying diagnoses causing pain Pain type (acute, neuropathic, visceral, etc.), intensity, impact on quality of life and function Medical comorbidities contributing to pain and/or affecting treatment: cardiovascular, cerebrovascular or neuromuscular diseases Medications that may interfere with the usual choices of drug or nondrug treatments. Psychosocial issues and patient's ability to cope with pain Factors that impact treatment planning and may affect response to treatment include depression, anxiety, negative emotions, past experiences, illness perception, alcohol dependence, substance abuse and current social situations. Clinical aspects Pain cannot be treated on the basis of pain intensity alone, for example with numeric based drug treatment algorithms like those commonly used for blood sugar or blood pressure. Rather, clinicians must respond to pain reports in a manner appropriate to the type of pain (e.g., acute versus chronic; neuropathic versus inflammatory) and setting (e.g., inpatient versus outpatient). THANK YOU !