1. Somatic sensation pain Is protective mechanism Occurs due to tissue damage Cause the individual to react to remove the painful stimulus For instance Sitting for a long time Ischemic pain  Weight shifting subconsciously Spinal cord injury If loose pain sense Fail to feel pain-fails to shift  Tissue breakdown and desquamation of the skin at the areas of pressure

2. Physiology of pain Definition An unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of such damage, or both

3. Types & qualities of pain 1. First pain a.k.a- sharp pain, pricking pain, acute pain, electric pain Felt 0.1 sec after painful stimulus application Not felt in most deeper tissues 2. Slow pain a.k.a slow burning pain, throbing pain, chronic pain, nausea pain occurs after 1 sec or more Associated with tissue destruction Leads to prolonged, unbearable suffering Occurs skin, deep tissues and organs

4. Physiology of pain Pain receptors Free nerve endings Location; superficial layers of skin, Internal tissues, Periosteum, arterial walls, joint surfaces etc Stimuli that excite pain receptors 1. Mechanical – fast & slow pain 2. Thermal- fast & slow pain 3. Chemical-slow pain Bradykinin Serotonin K+, acids, ach, proteolytic enzymes PG & substance p (cause pain indirectly by enhancing the sensitivity of pain endings )

5. Physiology of pain Non adapting nature of pain receptors Adapt very little, sometimes not at all Importance of non adaptation Allows the pain to keep the person appraised of a true damaging stimulation as long as it persist Hyperlagesia Increased sensitivity of pain receptors RATE OF TISSUE DAMAGE AS A STIMULUS FOR PAIN Temp. above 45 degrees centigrade Cause tissue damage Elicits painful stimulus Pain resulting from heat is closely correlated with the rate at which tissue damage is occurring

6. Physiology of pain Intensity of pain Is closely correlated with the rate of tissue damage from causes such as heat, bacterial infection, tissue ischemia etc Special importance of chemical painful stimulus Bradykinin is responsible for causing pain following tissue damage Mechanism of pain formation Pain intensity Correlates to local increase of K ions concentration & proteolytic enzymes that directly attack the nerves endings and excite pain by making the nerve membranes more permeable to ions 1. tissue ischemia acumulation of large amounts of lactic acid in the tissues Formed as a consequences of anaerobic metabolism (metabolism without oxygen) Chemical agents formed Bradykinin, proteolytic enzymes Formed in the tissues due to cell damage Stimulate pain nerve endings

7. Physiology of pain Mechanism of pain formation ctd 2. Muscle spasms Basis for many clinical pain syndromes a. Direct effect Muscle spasms stimulates mechanosensitive pain receptors b. Indirect Compress blood vessels causing tissue ischemia Increased metabolism in the muscle tissues Release of chemical pain inducing substances

8. Physiology of pain Pain signals transmission in CNS Dual pathways i. Fast sharp pain –pathway ii. Slow chronic pain –pathway Peripheral pain fibers- Fast & slow fibers Fast sharp pain signals Elicited by mechanical or thermal stimuli Transmitted in the peripheral nerves to the spinal cord Small type A-delta fibers Conduction velocity 6-30m/sec Slow chronic type of pain Eliciting stimuli- Chemical (commonest) and also Persisting mechanical & thermal stimuli Fibers transmitting type C fibers Conduction velocities 0.5 to 2m/sec

9. Physiology of pain Double pain sensation Occurs when sudden painful stimulus gives a double pain sensation It is common for a first sharp pain transmission to be followed by a slow pain transmission Cause: existence of the double system of pain innervations Sharp pain Appraises the person of a damaging influence Significance: make an individual to react immediately to remove himself /herself from the stimulus Slow pain Tends to become greater over time Produces intolerable suffering of long continued pain Makes the person keep trying to relieve the cause of pain

10. Physiology of pain Dual pathways in the cord & Brain stem On entering the cord - Pain signals takes two pathways to the brain 1. Neospanothalamic tract for fast pain First order neurons Terminates at lamina I- (lamina marginalis) of the spinal cord dorsal horns to synapse with the second order neurons Fibers fast type A delta Mechanical and acute thermal pain 2 nd order neurons Cross immediately to the opposite side of the cord thru the anterior commissure Turn upwards,passing thru the brain into anterolateral columns Termination Reticular areas of the brainstem (few fibers) Ventrobasal complex of the Thalamus -Most of the fibers-goes uninterrupted 3 rd order neurons : terminates in Somatosensory cortex & Other basal areas of the brain

11. Physiology of pain Body localization fast pain by CNS Exact localized compared to slow pain Poor localization occurs only When tactile receptors are stimulated (if information travels same tracts ) Yet when tactile receptors that excite DCML are simultaneously stimulated the localization can be nearly exact Neurotransmitter substance Glutamate is the substance secreted in the spinal cord at the type A delta nerve fiber endings Acts only for a few milliseconds 2.Paleospinothalamic – slow chronic pathway Pain transmitted from peripheral to spinal cord thru type C pain fibers as well as A delta fibers

12. Physiology of pain Peripheral fibers terminate in the spinal cord lamina II & III of the dorsal horns (substantial gelatinosa) Additional fibers enters lamina V Then the fibers join fast pain pathway passing thru the anterior commissure to opposite side of the cord Upward to brain in anterolateral pathway Neurotransmitter Substance P is the probable neurotransmitter of type C nerve endings Released much more slowly Builds up in conc. Over a period of seconds or even minutes Double pain sensation-Following pin prick Glutamate transmitter gives fast pain sensation Substance P transmitter gives more lagging sensation C fibers can also produce glutamate

13. Physiology of pain Projections of the paleospinothalamic pathway Slow chronic pain signals terminates in brain stem and thalamus 10-25 % pass to the thalamus Most terminate in Reticular nuclei (medulla, pons & mesencephalon) Tectal area of mesencephalon (deep to the superior & inferior colliculi) Periaqueductal gray –region surrounded the aqueduct of sylvius Areas concerned with feeling the suffering types of pain

14. Physiology of pain From brain stem areas Multiple short fiber neurons Relay pain signals upward Thalamus (intralaminar & ventrolateral nuclei) Hypothalamus (certain areas) Other basal regions of the brain Slow chronic pain Poorly localized Can only be localized to a major part of the body such as to one arm or leg But not to a specific point on the arm or leg Due to multisynaptic & diffuse connectivity of this pathway Appreciation /conscious perception of pain Pain perception is the principal function of the lower centers Functions of Reticular formation, thalamus Cerebral cortex Apart from pain perception, Plays an important role in interpreting of pain quality

15. Physiology of pain dual pathway for pain transmission

16. Physiology of pain Overall brain excitability by Pain signals Principal arousal system Reticular areas of brainstem & intralaminar nuclei of the thalamus Electrical stimulation leads to strong arousal effect on nervous activity through out the entire brain Thus pain signals – arouse overall brain excitability It is almost impossible for a person to sleep when is in severe pain

17. Physiology of pain Pain management 1. Surgically Interrupting pain pathways Cut pain nervous pathway at any one point “CORDOTOMY” Anterolateral sensory pathway cut in thoracic region deal with pain lower part of the body Relieve pain in patients with severe intractable pain such as cancer Failure 1. Uncrossed fibers 2. Sensitization of other pathways that normally are weak to be effectual e.g sparse pathways in the dorsal lateral 2.Cauterize – experimental specific pain areas in the intralaminar nuclei in the thalamus

18. Physiology of pain 3. Pain suppression – the Analgesia system Located in the brain and spinal cord Brain suppress pain signals input to the nervous system By activating pain control system- the analgesic system 3 major components 1. The periaqueductal grey & periventricular areas mesencephalon & upper pons  Neurons of this areas sends signals to 2. The raphe magnus nucleus (upper medulla & lower pons) and nucleus paragigantocellular (lateral medulla)  From these nuclei, send signals down the 3. dorsal columns in the spinal cord to A pain inhibitory complex located in dorsal horns of the spinal cord Site of blocking the pain before it is relayed to the brain

19. Physiology of pain Electricle stimulation of either periaqueduactal grey area or raphe magnus nucleus can suppress many strong pain signals entering by way of the dorsal spinal roots Also stimulation of higher brain center areas such as periventricular nuclei in the hypothalamus Medial forebrain forebrain bundle in the hypothalamus that excite periaqueductal grey thereby suppressing pain Transmitters involved in analgesia system Encephalin Encephalin released by fibers originating in the periventricular & the periaqueductal grey on stimulation Cause the dorsal horns spinal cord to release serotonin at their nerve endings Serotonin

20. Physiology of pain Serotonin cause local cord neurons to secrete encephalin as well Which causes both presynaptic and postsynaptic inhibition of incoming type c and A delta pain fibers when they synapse at the dorsal horn 4. Brain opiate system endorphins and encephalins 1. activation of the analgesia system by nervous signals entering the periaqueductal grey and periventricular areas OR 2.inactivation of pain pathway by morphine like drugs can almost totally suppress many pain signals entering thru the peripheral nerves

21. Physiology of pain Morphine like agents –mainly opiates Acts at many other points in the analgesia system including the dorsal horns of the spinal cord Opiates like substances Beta endorphins (produced by hypothalamus & pituitary glands) Met encephalin Leu encephalin Dynorphin Also they are found in brain stem and spinal cord in the portion of analgesia system

22. Physiology of pain Others 1. simultaneously tactile sensory signals Can inhibit pain transmission stimulation of large type A beta sensory fibers from peripheral tactile receptors can depress transmission of pain signals from the same body area Mechanism : local lateral inhibition in the spinal cord 2. psychogenic excitation of the central analgesia system 1& 2 forms the basis for pain relief by acupuncture 3. Treatment /suppression of pain by electrical stimulation Clinical procedure Stimulating electrodes are..

23. 1. Placed on selected areas of skin 2. Implanted over the spinal cord-stimulate the dorsal sensory columns 3. Placed in Intralaminar nuclei of the thalamus 4. Periventricular or periaqueductal area of the diencephalon  The Patient can then personally control the degree of stimulation  Few minutes of stimulation can bring dramatic relief which can last for as long as 24 hours Physiology of pain

24. Referred pain Is the feeling of pain in a part of the body that is fairly remote from tissue causing the pain For instance Pain in visceral organs referred to an area on the body surface

25. Physiology of pain Referred pain Mechanism Branches of visceral pain fibers synapse in the spinal cord on the same second order neurons that receives pain signals from the skin Thus a person has the feeling that sensation originate in the skin itself

26. Referred Pain: Heart

27. Clinical abnormalities of pain Hyperalgesia Excessive excitability of pain nervous pathway Cause 1. Primary hyperalgesia Excessive sensitivity of sun burned skin which results from sensitization of the skin pain endings by local tissue products from the burn e.g histamine, PG 2. Secondary hyperalgesia Facilitation of sensory transmission e.g lessions in the spinal cord or thalamus

28. Physiology of pain Herpes zoster (shingles) Herpes virus infects a dorsal root ganglion Causing severe pain in the dermatomal segment subserved by the ganglion Pain is caused by the infection of the pain neuronal cells in the dorsal root ganglion by the virus