Fotografia programu Photo Editor: PAIN And its Pathophysiology Dr.Abhijit Gogoi University of Fiji PAIN And its Pathophysiology : Definitions of pain • Pain is a complex unpleasant phenomenon composed of sensory experiences that include time, space, intensity, emotion, cognition, and motivation • Pain is an unpleasant or emotional experience originating in real or potential damaged tissue • Pain is an unpleasant phenomenon that is uniquely experienced by each individual ; it cannot be adequately defined, identified, or measured by an observer PowerPoint Presentation: The experience of pain Three systems interact usually to produce pain: 1. sensory - discriminative 2. motivational - affective 3. cognitive - evaluative 1. Sensory - discriminative system processes information about t he strength, intensity, quality and temporal and spatial aspects of pain 2. Motivational - affective system determines the individual´s approach-avoidance behaviours 3. Cognitive - evaluative system overlies the individuals learned behaviour concerning the experience of pain. It may block, modulate, or enhance the perception of pain PowerPoint Presentation: Pain c ategories Somatogenic pain is pain with cause (usually known) localised in the body tissue a/ nociceptive pain b/ neuropatic pain 2 . Psychogenic pain is pain for which there is no known physical cause but processing of sensitive information in CNS is dysturbed Acute and c hronic p ain Acute pain is a protective mechanism that alerts the individual to a condition or experience that is immediately harmful to the body Onset - usually sudden PowerPoint Presentation: Relief - after the chemical mediators that stimulate the nociceptors , are removed • This type of pain mobilises the individual to prompt action to relief it • Stimulation of autonomic nervous system can be observed during this type of pain ( mydriasis, tachycardia, tachypnoe, sweating, vasoconstriction) Responses to acute pain - increased heart rate - diaphoresis - increased respiratory rate - blood sugar - elevated blood pressure - gastric acid secretion - pallor or flushing , - gastric motility dilated pupils - blood flow to the viscera , kidney and skin - nausea occasionally occurs PowerPoint Presentation: Psychological and behavioural response to acute pain fear - general sense of unpleasantness o r unease - anxiety Chronic pain is persistent or intermittent usually defined as lasting at least 6 months The cause is often unknown , often develops insidiously, v ery often is associated with a sense of hopelessness and helplessness. Depression often results PowerPoint Presentation: Psychological response to chronic pain Intermittent pain produces a physiologic response similar to acute pain. Persistent pain allows for adaptation (functions of the body are normal but the pain is not reliefed) Chronic pain produces significant behavioural and psychological changes The main changes are: - depression - an attempt to keep pain - related behaviour to a minimum - sleeping disorders - preoccupation with the pain - tendency to deny pain PowerPoint Presentation: Neuroanatomy of p ain The portions of the nervous system responsible for the sensation and perception of pain may be divided into three areas: 1. afferent pathways 2. CNS 3. efferent pathways The afferent portion is composed of: a) nociceptors (pain receptors) b) afferent nerv fibres c) spinal cord network PowerPoint Presentation: The brain first perceives the sensation of pain • The thalamus, sensitive cortex : perceiving describing of pain localising • Parts of thalamus, brainstem and reticular formation: - identify dull longer-lasting, and diffuse pain • The reticular formation and limbic system: - control the emotional and affective response to pain Because the cortex, thalamus and brainstem ar e interconnected with the hypothalamus and autonomic nervous system, the perception of pain is associated with an autonomic response PowerPoint Presentation: The r ole of the a fferent and e fferent p athways in processing of pain information Nociceptive pain Nociceptors: End ing s of small unmyelinated and lightly myelinated afferent neurons Stimulators: C hemical, mechanical and thermal noxae Mild stimulation positive, pleasurable sensation (e.g. tickling) Strong stimulation pain Th ese differences are a result of the frequency and amplitude of the afferent signal transmitted from the nerve endings to the CNS Location : I n muscles, tendons, epidermis , subcutanous tissue, visceral organs - they are not evenly distributed in the body (in skin more then in internal structures ) PowerPoint Presentation: Afferent pathways : • From nociceptors transmitted by small A-delta fibers and C - fibers to the spinal cord form synapses with neurons in the dorsal horn (DH) • From DH transmitted to higher parts of the spinal cord and to the rest of the CNS by spinothalamic tracts * The small unmyelinated C - neurons are responsible for the transmission of diffuse burning or aching sensations * Transmission through the larger, myelinated A - delta fibers occurs much more quickly. A - fibers carry well-localized, sharp pain sensations PowerPoint Presentation: E fferent analgesic system Its role: - inhibition of afferent pain signals Mechanisms: - pain a fferent s stimula tes the neurons in periaqueductal gray ( PAG ) - gray matter surrounding the cerebral aqueduct in the midbrain results in activation of efferent (descendent) anti-nociceptive pathways - f rom there the impulse s are transmitted through the spinal cord to the dorsal horn - there thay inhibit or block transmission of nociceptive signals at the level of dorsal horn PowerPoint Presentation: The role of the spinal cord in pain processing • Most afferent pain fibers terminate in the dorsal horn of the spinal segment that they enter. Some, however , extend toward the head or the foot for several segments before terminating • The A - fibers , some large A-delta fibers and small C - fibers terminate in the laminae of dorsal horn and in the substantia gelatinosa • The laminae than transmit specific information (about burned or crushed skin, about gentle pressure) to 2nd afferent neuron PowerPoint Presentation: • 2 nd afferent neurons transmit the impulse from the substantia gelatinosa (SG) and laminae through the ventral and lateral horn , crossing in the same or adjacent spinal segment , to the other side of the cord . From there the impulse is carried through the spinothalamic tract to the brain. The two divisions of spinothalamic tract are known: the neospinothalamic tract - it carries information to the mid brain, thalamus and post central gyrus (where pain is perceived) 2. the paleospinothalamic tract - it carries information to the reticular formation, pons, limbic system, and mid brain (more synapses to different structures of brain) PowerPoint Presentation: Theory of p ain production and modulation • Most rational explanation of pain production and modulation is based on gate control theory (created by Melzack and Wall ) • According to this theory, nociceptive impulses are transmitted to the spinal cord through large A - delta and small C - fibers • These fibers create synapses in the SG • The cells in this structure function as a gate , regulating transmission of impulses to CNS Stimulation of larger nerve fibers (A-alfa, A-beta) causes the cells in SG to "close the gate". • A closed gate decreases stimulation of T-cells (the 2 nd afferent neuron) , which decrease s transmission of impulses, and diminishes pain perception PowerPoint Presentation: Stimulation of s mall fiber input inhibits cells in SG and "open the gate". • An open gate increases the stimulation of T-cells transmission of impulses enhances pain perception • In addition to gate control through large and small fibers stimulation, the central nervous system, through efferent pathways, may close, partially close, or open gate. Cognitive functioning may thus modulate pain perception Action of endorphins (ED) All ED act by attaching to opiate receptors on the plasma membrane of the afferent neuron . The result than is inhibition of releasing of the neurotransmitter, thus blocking the transmission of the painful stimulus PowerPoint Presentation: Neuropathic pain It occurs as a result of injury to or dysfunction of the nervous system itself, peripheral or central Deaferentation pain - form of neuropathic pain: a term implying that sensory deficit in the painful area is a prominent feature ( anesthesia dolorosa ) • Phantom pain- pain localizei into non-existing organ (tissue) • Long-lasting pain after short-lasting pain stimulus PowerPoint Presentation: What causes neuropathic pain? Neuropathic pain often seems to have no obvious cause; but, some common causes of neuropathic pain include : Alcoholism , Amputation, Back, Leg, and Hip problems, Chemotherapy , Diabetes mellitus, Facial nerve problems , HIV infection or AIDS Multiple sclerosis , Shingles (Herpes yoster), Spine surgery What are the symptoms of neuropathic pain? Symptoms may include: Shooting and burning pain, Tingling and numbness PowerPoint Presentation: Allodynia - phenomenon characterised by painful sensations provoked by non - noxious stimuli, ( e.g. touch ) , transmitted by fast- conducting nerve fibres Mechanism: changes of the response characteristics of seco nd - order spinal neurons so that normally inactive or weak synaptic contact mediating non - noxius stimuli acquire the capability to activate a neuron that normally responds only to impulses signaling pain • Hypersensitivity – increased sensitivity of the system involved in the pain processing • Hyperalgesia – increased the pain sensitivity to noxious stimuli PowerPoint Presentation: Acute Pain We can distinguish two types of acute pain : 1. Somatic 2. Visceral – r eferred Somatic pain is superficial coming from the skin or close to the surface of the body. Visceral pain refers to pain in internal organs, the abdomen, o r chest . Referred pain is pain that is present in an area removed or distant from its point of origin . The area of referred pain is supplied by the nerves from the same spinal segment as the actual site of pain . Clinical Manifestation of Pain PowerPoint Presentation: Different types of chronic somatic pain I. Nervous system intact 1. nociceptive pain 2. nociceptive - neurogenic pain (nerve trunk pain ) II. Permanent functional and/or morphological abnormalities of the nervous system (preganglionic, spinal - supraspinal) 1. neurogenic pain 2. neuropathic pain 3. deafferentation pain PowerPoint Presentation: The most common chronic pain Persistent low back pain – result of poor muscle tone,inactivity, muscle strain , sudden vigorous exercise 2. Chronic pain associated with cancer PowerPoint Presentation: 3. Neuralgias - results from damages of peripheral nerves a) Causalgia - severe burning pain appearing 1 to 2 weeks after the nerve injury associated with discoloration and changes in the texture of the skin in the affected area. b) Reflex sympathetic dystrophies - occur after peripheral nerve injury and is characterised by continuous sever e burning pain . Vasomotor changes are present (vasodilatation vasoconstriction cool cyanotic and edematous extremities). 4. Myofascial pain syndromes - second most common cause of chronic pain. These conditions include: myositis, fibrositis, myalgia, muscle strain, injury to the muscle and fascia The pain is a result of muscle spasm, tenderness and stiffness PowerPoint Presentation: 5. Hemiagnosia – is a loss of ability to identify the sorce of pain on one side (the affected side) of the body . Application of painful stimuli to the affected side thus produces anxiety, moaning, agitation and distress but no attem p t to withdrawal from or push aside the offending stimulus. Emotional and autonomic responses to the pain my be intensified. ● Hemiagnosia is associated with stroke that produces paralysis and hypersensitivity to pain ful stimuli in the affected side 6. Phantom limb pain - is pain that an individual feels in amputated limb PowerPoint Presentation: Pathophysiology of muscle pain Muscle pain - a part of somatic deep pain , (MP) - it is common in rheumathology and sports medicine - is rather diffuse and difficult to locate MP is not a prominent feature of the serious progressive diseases affecting muscle, e.g. the muscular dystrophies, denervation , or metabolic myopathies, but it is a feature of rhabdomyolysis Muscles are relatively insensitive to pain when elicited by needle prick or knife cut , but overlying fascia is very sensitive to pain . Events, processes which may lead to muscular pain are: ● metabolic events: • metabolic depletion ( ATP muscular contract ure) • accumulation of unwanted metabolities (K + , bradykinin) PowerPoint Presentation: Pathophysiology of visceral pain Visceral pain: T ypes - angina pectoris, myocardial infarction, acute pancreatitis, cephalic pain, prostatic pain, ne phr lolytiatic 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 PowerPoint Presentation: Adequate stimuli of inducing visceral pain: 1. abnormal distention and contraction of the hollow viscera muscle walls 2. rapid stretching of the capsule of such solid visceral organs as are the liver, spleen, pancreas... 3. abrupt anoxemia of visceral muscles 4. formation and accumulation of pain - producing substances 5. direct action of chemical stimuli (oesophagus, stomach ) 6. traction or compression of ligaments and vessels 7. inflammatory processes 8. necrosis of some structures (myocardium, pancreas) PowerPoint Presentation: Characteristic feature of true visceral pain a) it is dull, deep, not well defined, and differently described by the patients b) sometimes it is difficult to locate this type of pain because it tends to i r r adiate c) it is often accompanied by a sense of malaise d) it induces strong autonomic reflex phenomena (much more pronounced than in pain of somatic origin) - diffuse sweating, vasomotor responses, changes of arterial pressure and heart rate, and an intense psychic alarm reaction - "angor animi" - in angina pectoris) • There are many visceral sensation that are unpleasant but below the level of pain , e.g. feeling of disagreeable fullness or acidity of the stomach or undefined and unpleasant thoracic or abdominal sensation. These visceral sensation may precede the onset of visceral pain PowerPoint Presentation: Refered visceral pain (transferred pain) Refered pain = when an algogenic process affecting a viscus recurs frequently or becomes more intense and prolonged, the location becomes more exact and the painfull sensation is progressively felt in more superficial struftures ● Refered pain may be accompanied by allodynia and cutaneous and muscular hyperalgesia Mechanisms involved in refered pain creation: a) 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. b) senzitization of neurons in dorsal horn PowerPoint Presentation: Painful v isceral 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 reffered 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 PowerPoint Presentation: Disturbances in p ain p erception and n ociception Most of the disturbances are congenital Congenital analgesia - nociceptive stimuli are not processed and/or integrated at a level of brain. Patient does not feel a pain b) Congenital sensoric neuropathy - nociceptive stimuli are not transmitted by peripheral nerves or by spinal afferent tracts . Acquired disturbances in pain perception and nociception They may occur at syringomyely , disturbances of parietal lobe of brain, in patients suffering from neuropathy (e.g. chronic diabetes mellitus) PowerPoint Presentation: DESCENDING TRACTS DESCENDING TRACTS: Fiber Types A Fibers: Somatic, myelinated. Alpha ( α ): Largest, also referred to as Type I. Beta ( β ): Also referred to as Type II. Gamma ( γ ): Delta ( δ ): Smallest, referred to as Type IV. Fiber Types: Fiber Types B Fibers: Lightly myelinated. Preganglionic fibers of ANS. C Fibers: Unmyelinated. Found in somatic and autonomic systems. Also referred to as Type IV fibers. Fiber Types: Fiber Types Sensory fibers are either: A- α or A- β fibers: Conduction rate = 30-120 m/sec. A- δ fibers: Conduction rate = 4-30 m/sec. C fibers: Conduction rate is less than 2.5m/sec. Fiber Types: Fiber Types Nociceptors and thermoreceptors are related to C fibers or A- δ fibers.