Anatomy and physiology of pain

1. Anatomy and physiology of pain

2. Nociceptive 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.

3. 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 involves4 basicprocesses • transduction • transmission • perception of pain • modulation of pain

4. Nociceptors • Tissue injury activates primary afferent neurons called nociceptors,which are small diameter afferent neurons (with A-delta and C-fibers)

5. Nociceptors • Nociceptors respond to noxious stimuli • Nociceptors are found in • skin • muscle • joints • and some visceral tissues.

6. Nociceptors Nociceptive primary afferent neurons are varied: • most are “silent”(may not respond to standard stimuli, only than inflammatory substances are present) • some are specificto 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

7. Nociceptors • nociceptors free nerve endings has capacity to distinguish between noxious and innocuous stimuli whenexposed 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 impulseto the spinal cord

9. Substances released • 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 developmentof new analgesic drugs

10. Clinical significance • 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.

16. Transduction • 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.

17. 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.

19. Transmission • once depolarization occurs, • transmission of information proceeds proximally along the axon to the spinal cord and then on to higher centers.

21. transmission across the first central synapse may be influenced by activity in the primary afferent itself and modulatoryneural pathways. • that originate segmentally or supraspinally. • further modulation results from processes initated by glial cells. Transmission

22. 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

23. Clinical significance

24. Clinical significance

25. Clinical significance

26. Perception of pain • 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 signalsmay get through the gate, leaving limited signals (such as pain) to be transmitted to the higher structures.

29. Perception of pain

30. Modulation 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.

31. Modulation of pain • The endorphinergic pain modulatory pathways are characterizedby 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 opioidligands. Most of the drugs used for pain are full mu receptor agonists.

32. 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.

33. 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.

34. 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 toinduce cutaneous pain are not algogenicinthe viscera. This explains why in the past the viscera wereconsidered to be insensitive to pain.

35. 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)

37. 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 focusin the segment at which they enter the spinal cord. • afferent impulses from the skin entering the same segment are therebyfacilitated, giving rise to true cutaneous pain. • senzitization of neurons in dorsal horn

38. 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

39. Referred visceral pain

40. Clinical aspects • 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.

41. 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 variableinterval. • 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.

42. EVALUATION OF PAIN

43. EXPERIMENTAL EVALUATION OF PAIN

44. Somatic pain models Hot plate test Tail flick test Tail immersion test Analgezimeter test

45. Visceralpain models Writhing test Capsaicin colon stimulation test Inflammatory cystitis test (clyclophosphamide)

46. Behavioural models Activity cage test Hole board test

47. Inflammation models Subcutaneous pellets implantation Pletismometer test

48. !!! The results obtained in experiments can not be directly extrapolated in humans   

49. CLINICAL EVALUATION OF PAIN

50. Pain history • Description: severity, quality, location, temporal features, frequency, aggravating & alleviating factors • Previous history • Context: social, cultural, emotional, spiritual factors • Meaning • Interventions: what has been tried?