﴿و ما أوتيتم من العلم إلا قليلا﴾ بسم الله الرحمن الرحيم ﴿و ما أوتيتم من العلم إلا قليلا﴾ صدق الله العظيم الاسراء اية 58

Assist Prof. of Medical Physiology Physiology of Pain and Pain Control System By Dr. Abdel Aziz M. Hussein Assist Prof. of Medical Physiology

Pain Sensation Def : Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage Significance: Pain is a warning signal for tissue damage. It is the prominent symptom of tissue damage Pain has a protective function. It initiates protective reflexes that; Get rid of the painful stimulus. Minimize tissue injury or damage.

Classification of Pain

Occurs at the time of injury Pain Sensation A) According to its duration: Pain is classified into 2 types; 1. Acute Fast or epicritc Occurs at the time of injury 2. Chronic Slow or protopathic After injury

Pain Sensation Cutaneous pain Deep pain Visceral pain B) According to site of origin: 3 types; Cutaneous pain From skin and subcutaneous tissues Usually pricking or burning pain Deep pain From structures deep to the skin e.g. skeletal ms, joints, and tendons Usually dull aching or throbbing Visceral pain From internal viscera e.g. stomach Usually colicky or dull aching

Pain Sensation 1. Physiological Pain 2. Pathological Pain C) According to its mechanism or cause: Pain is classified into 2 main types; 1. Physiological Pain Also called Nociceptive pain Caused by stimulation of pain receptors by tissues damage e.g. in inflammation 2. Pathological Pain Also called neuropathic pain Caused by damage of nerve pathway e.g. sciatica

Pain Perception

Pain Perception Pain sensation Painful stimulus

Pain Receptors 1) Morphology: are specific free nerve endings Pain Rs are morphologically similar but functionally they are specific 1) Morphology: are specific free nerve endings 2) Highly specific i.e. respond to tissue damage only Classified according to their adequate stimulus into:- a) Mechanical Pain Rs: Respond to strong mechanical trauma e.g. cutting b) Thermosensitive pain Rs: Respond to excessive changes in temp (above 45°C and below 10°C). c) Chemical Pain Rs: respond to noxious chemical stimuli. d) Polymodal Pain Rs: respond to a combination of mechanical, thermal, and chemical noxious stimuli

Pain Receptors 3) Distribution: Abundant in the skin and some internal tissue such as the periosteum, arterial wall, joint surfaces, and the dura of the tentorium cerebelli. Few in deep tissues and all viscera. So, for pain to occur, painful stimulus must by intense and widespread. The deep & visceral pain is poorly localized. Brain itself and the parenchymal tissues of the liver, kidneys, and lungs have no pain receptors “pain insensitive structures”

Pain Receptors 4) Threshold : It is the lowest intensity of injurious agent needed to stimulate the pain receptors to cause pain sensation Pain receptors are of high threshold: the pain receptors needs sufficient degree of tissue damage to be stimulated. Measured by; By pricking the skin with a pin at measured levels. By compressing the skin against hard objects. Thermal method (more accurate) (45 C)

Pain Receptors 5) Adaptation: Slowly adapting receptors even non adapting receptors This is very important because it directs the subject to get rid of the injurious agent

Pain Receptors 6) Mechanism of stimulation: Tissue damage Chemical stimuli Strong acids or Alkalies Mechanical stimuli Cutting or pricking Thermal stimuli temp. > 45 C and < 10 C Tissue damage 1st class K ions, Histamine, Serotonin, and Bradykinin Release of Pain Producing Compounds (PPS) 2nd class PGE2, leukotriens and Substance P Sensitize the pain Rs by lowering its threshold to stimuli Directly stimulate Pain Receptors

Neural Pathways of Pain

Fast Pain Pathway Pathway: Neospinothalamic tract A) 1st order neuron : A delta afferent fibers End in lamina I of dorsal horn of spinal cord B) 2nd order neuron : Axons of neurons lamina I of dorsal horn of spinal cord cross the opposite side in front of central canal and ascend as neospinothalamic in spinal cord and as spinal leminiscus in brain stem End in posteroventral nucleus of thalamus (PVNT)

Fast Pain Pathway Pathway: C) 3rd order neuron : Axons of neurons of PVNT ascend in sensory radiations End in primary somatic sensory area (area 3,1,2) Note: The chemical transmitter released at the central end of A delta fibers that carry fast pain is glutamate

Receptors Free nerve endings Lateral spinothalamic tract Fast Pain Pathway PVNT Sensory Radiations Spinal Leminiscus Lamina I A delta Receptors Free nerve endings Lateral spinothalamic tract

Slow Pain Pathway Pathway: Paleospinothalamic tract A) 1st order neuron : C afferent fibers End in lamina II and III (called substantia Gelatinosa of Rolandi SGR) of dorsal horn of spinal cord B) 2nd order neuron : Axons of neurons SGR of dorsal horn of spinal cord cross the opposite side in front of central canal and ascend in spinal cord and as; Spinoreticular tract end in RF of MO and Pons Spinotectal tract end in PAG areas of midbrain Paleospinothalamic tract end in non specific thalamic nuclei (intralaminar and midline)

Slow Pain Pathway Pathway: C) 3rd order neuron : Axons of neurons from RF and NSTN of thalamus ascend in sensory radiations Terminate diffusely in all areas of the cerebral cortex Note: The chemical transmitter released at the central end of c fibers that carry fast pain is substance P

Paleospinothalamic tracts All cortical areas Non-specific nuclei of thalamus Periaqueductal gray area (PAG) in midbrain Reticular formation In MO and Pons SGR Laminae II, III Afferent C fibers Receptors Free nerve endings Paleospinothalamic tracts

Significance of Pain Pathways Paleospinothalamic Neospinothalamic a) Continuously inform the C.N.S about the presence of tissue damage → direct the person to remove the injurious agents. a) Rapidly inform the C.N.S about the injurious agent → initiate rapid protective reflexes as flexion withdrawal reflex. b) Strong arousal state due to potent activation of RAS c) Initiation of the emotional & autonomic reactions, through RF b) Determines accurately the site “locality” of the painful stimuli.

Comparisons Between Slow and Fast Pain Chronic (Slow) Acute (Fast) Skin, deep tissues, and viscera Skin only Source Burning Pricking Quality One or more seconds after stimulation Within 0.1 sec after stimulation Onset Long (few minutes) Short (one second) Duration Diffuse Well –localized Localization C A-delta Afferent Paleospinothalamic tract Neospinothalamic tract Tract Thalamus Cerebral cortex Centre Substance P Glutamate Chemical trans.

Radiating and Referred Pain

Referred Pain Def: Referred pain is pain felt away from the site of its origin Radiating pain is pain appear to migrate away from the its original site e.g. sciatic pain Referred pain is a part of radiating pain N.B. Visceral pain usually referred, deep pain may be referred but cutaneous pain never referred

Referred Pain Site of referral is determined by dermatomal rule: The pain from a viscera is referred to a somatic structure (skin or deep structure) which were developed in the same embryonic segment and supplied by the same dorsal root ganglia. Abnormal sites are due to migration of viscera.

Pain Injury

Referred Pain Mechanism : Convergence Projection Theory: Afferents pain fibers from skin area and diseased viscera converge on the same neuron of SGR and finally stimulate the same cortical neuron The cortex project (feel) pain as it is coming from the skin because the sensory cortex is accustomed to receive pain from the skin Convergence may occurs also at the level of thalamus or sensory cortex

Neuropathic Pain Def. : Is a chronic type of pain caused by damage to or pathological changes in the nerve fibers either in the peripheral or central nervous system. Examples: Central → Central pain e.g. thalamic infarct Peripheral → e.g. nerve compression e.g. Sciatica (Lesley Smith), neuralgias and neuropathy Mixed → e.g. post herpetic neuralgia.

Nociceptive pain Neuropathic Pain

Neuropathic Pain Characters: 1. Described as tingling, numbness, , burning or shooting pain. 2. It occurs in bouts or paroxysms. 3. Usually accompanied by hyperalgasia and allodynia. 4. Hardly to be treated. 5. Partially responsive to opioid therapy 6. May respond to tricyclic antidepressant

Pain Control System

Pain Control System 1) Def, System which control pain transmission in CNS or inhibit pain transmission i.e. endogenous analgesia system N.B The activity of this system differs from one person to another and from time to time in the same person.

2) Components : 1. Periventricular hypothalamic area 2. Periaqueductal area (PAG) 3. Nucleus reticularis paragigantocellularis (NRPG) and locus cerulus 3. Nucleus raphe magnus (NRM) 4. Pain Inhibitory Complex (PIC)

Endogenous Analgesia System 3) Neurochemistry: This system act through the release of endogenous opioid peptides which act on opiate receptors. Opioid peptides: They include 3 groups; enkephalins, endorphins and dynorphins. Opiate Receptors: 3 types of opiate receptors : delta (δ), kappa (κ), and mu (μ). Enkephalins bind with the delta (δ) receptors Endorphins bind with the mu (μ) receptors Dynorphins bind with the kappa (κ) receptors. These receptors can be blocked by naloxone, which is a morphine antagonist

Activation of the Pain Control System Clinical (Experimental) Natural (physiological) 1- Electrical stimulation of certain regions of pain control system Exposure to severe stress, particularly when associated with strong emotional excitement. 2- Local application of opiates (such as morphine) at particular regions in the nervous system. (pharmacological analgesia) Stress induced analgesia

Mechanism of Stress Induced Analgesia

Posterior horn of spinal cord Ascending pathway 1st order neuron of pain Glutamate Substance P Posterior horn of spinal cord

Posterior horn of spinal cord Limbic system RF Hypothalamus Cerebral cortex PAG Severe stress Strong emotions Encephalin ++ NRM LC Serotonin ++ Noradrenaline ++ Ascending pathway 1st order neuron of pain Encephalins -- Glutamate Substance P Posterior horn of spinal cord

Action of encephalins at PIC

Gate Control Theory

Gate Theory of Pain Sites: Was proposed by Melzack and Wall in 1965. States that, the sites of synapses along the pain pathway are considered as gates through which pain transmission can be; Facilitated (if the gate is open) or Blocked (if the gate is closed). Sites: The main pain gates are: 1- Spinal gate: at the SGR. 2- Brain stem gate: at the nuclei of reticular formation. 3- Thalamic gate: At neurons of PVLNT & intalaminar thalamic nuclei.

3 2 1

Spinal Gate At spinal gate pain transmission is blocked by; Descending inhibitory impulses through the pain control system activating enkephalin-secreting interneuron Stimulation of the large diameter nerve fibers (A delta and A beta) terminating peripherally in mechanoreceptors, such as tactile receptors or proprioceptors (A beta), and pricking pain fibers (A delta).

Gate Theory of Pain

Spinal Gate This may explain why simple maneuvers such as rubbing the skin (thus exciting tactile and pressure receptors), near a painful area is often effective in relieving certain types of pain → A beta Also block of pain by acupuncture (A delta fibers)

Pain Control by Rubbing Interneuron Rubbing of the skin A beta fibers Pain C fiber Painful stimuli

Acupuncture Interneuron A delta fibers Pain C fiber Painful stimuli

Applications of Gate Control Theory This theory provides basis for various methods of pain relief Massaging a painful area Applying irritable substances to a painful area (counter-irritation) Transcutaneous Electrical Nerve Stimulation (TENS) Acupuncture

Acupuncture Mechanism: Acupuncture has been practiced in China for more than 4000 years as a method for pain relief. Mechanism: 1- Needles in appropriate body regions are thought to excite certain sensory neural pathways which feed into the brain stem centers (such as the PAG) involved in the pain control system, with release of endogenous opioid peptides. 2- Simultaneous suppression of pain transmission at the spinal pain-gate by acupuncture

TENS Def., TENS is any stimulating device which delivers electrical currents across the intact surface of the skin Mechanism: TENS causes relieve of pain by activate large diameter ‘touch’ fibres (Aβ) without activating smaller diameter nociceptive fibres (Aδ and C) this causes; 1- Excitation of certain sensory neural pathways which activate PAG area involved in the pain control system, with release of endogenous opioid peptides. 2- Simultaneous suppression of pain transmission at the spinal pain-gate by acupuncture

TENS

Modulation of Pain Perception Conditions that closes the Gate Conditions that open the Gate medications Counter stimulation, e.g. massage, heat Extent of injury Extra activity Physical conditions Relaxation Positive emotion Depression, tension Anxiety, worry Emotional conditions Distraction Involvement in life activity Focusing on pain Mental conditions

THANKS