PAIN• An unpleasant sensory and emotionalexperience associated with actual or potentialtissue damage, or described in terms of suchdamage.– (International association for the study of pain1979)
Damaged tissues release proteolytic enzymes, K+&histamine .Proteolytic enzymes act on globulins in theinterstitial Fluid to release kinins.e.g bradykinin, K+ and histamine stimulate pain receptorsPain is a protective sensation.
Distribution of pain receptors- More : Skin, periosteum, arteries, joint surfaces, &tentorium cerebelli and cranial sinuses.- Less : deep tissues.- Absent : liver parenchyma, lung alveoli and brain.►Nerve fibres: A delta and C fibres.►Adaptation: Slowly (static-tonic) or nonadaptivereceptors.
Types of painPain is classified according to the:(a) Site of pain1. Cutaneous pain.2. Deep pain.3. Visceral pain.(b) Quality of pain1. Epicritic i.e sharp pricking pain.2. Protopathic i.e dull aching pain.3. Burning pain.
Pain nerve fibers – fast pain and slow pain• From the pain receptors, the pain stimulus istransmitted through peripheral nerves to thespinal cord and from there to the brain. Thishappens through two different types of nervesfibers:• A-delta "fast pain” and• C-fibers “slow pain” nerve fibers.
What is “fast pain” and “slow pain”?• A pain stimulus, e.g. if you cut yourself,consists of two sensations.• first “fast pain” sensation-is experienced assharp.• “slow pain”, more a dull and burning.• Occurs after a short time• lasts a few days or weeks,• Chronic pain-if inappropriately processed bythe body, it can last several months
Fast pain• nerves are called A-delta fibers.• relatively thick size nerve fibers allow the painstimulus to be transferred very fast (at a speedof five to 30 meter/second), hence the name• This is all to make the body withdrawimmediately from the painful and harmfulstimulus, in order to avoid further damage.
Slow Pain• starts immediately after the fast pain• is transmitted by very thin nerve fibers, calledC-nerve fibers (their diameter is between 0.2to 1 thousandth of a millimeter).• pain impulse can only be transmitted slowly tothe brain, at a speed of less than 2 meters persecond.• Body response -immobilization (guarding,spasm or rigidity), so that healing can takeplace.
(1) Cutaneous Pain• Fast (Immediate, acute• sharp or pricking)• Felts within 0.1 sec ond .• Short-duration.• Mechanical &Thermal R.• A delta fibres.• Ends in cerebral cortex.• Well localized.• Not felt in deep tissues• Blocked by hypoxia & pressure• Neospinothalamic tract• Neurotransmitter:• Glutamate .• Slow (Chronic, burning, achingthrobbing nauseous)After one second .Prolonged;annoying,intolerable.Elicited by All types of R.C fibresEnds in non specific thalamicnuclei & Reticular formation.Poorly localized .Occurs in skin & deep tissuesBlocked by local anesthesia.Paleospinthalamic tractNeurotransmitterSubstance P.
Nociceptive Pathways• Fast• A Delta Fibers• Glutamate• Neospinothalamic• Mechanical, Thermal• Good Localization• Sharp, Pricking• Terminate in VBComplex of Thalamus• Slow• C Fibers• Substance P• Paleospinothalamic• Polymodal/Chemical• Poor Localization• Dull, Burning, Aching• Terminate; RF– Tectal Area of Mesen.– Periaqueductal Gray
Appreciation of pain- Fast pain; is appreciated in thalamus and cortex.- Slow pain; is appreciated mainly in thalamus.Functions of the cortex in pain appreciation1. Localization of pain 2. Discrimination of type of pain.3. Modulation of pain by emotional and behavioral factors.
Arousal reaction to pain signalsThe non specific thalamic nuclei (intra-laminarnuclei) and reticular formation have a strongarousal effect on the brain which prevents sleepduring pain.
Deep pain C. FibresDiffuse, Dull aching and Depressor effects.Causes: - inflammation, ischaemia or muscle spasm.- Bone fractures; due to stimulation of periosteal painreceptors.Characters of deep pain1. Dull aching or rhythmic cramps.2. Diffuse (poorly localized).Depressor autonomic changes: decreased heart rate,decreased arterial blood pressure ,nausea & vomiting.
DEEP PAIN• Arises from Periosteum & Ligaments• Continuous Contraction of Muscles• Poorly Localized• Associated with Sweating & Changes in BloodPressure• Often Nauseating• Transmitted via Antero Lateral System
Ischaemic painType of deep pain felt in muscles when their bloodsupply is decreased.The Patients complains of severe pain in the musclesupon walking or running due to accumulation of painproducing substances as lactic acid.Examples1. Cardiac muscle: angina pectoris.2. Skeletal muscle: intermittent claudication.
Visceral pain C FibresMost of viscera contain only pain receptors.Pain from viscera is carried a long; C fibres.Pain from peritoneum, pleura or pericardium:Adelta.It differs from cutaneous pain. Sharp cut in the viscera does not cause pain (why).. Diffuse stimulation of pain nerve ending ® severe pain.
Causes Of Visceral Pain1. Ischaemia: increased acidic metabolites, bradykinin &proteolytic enzymes.2. Inflammation of peritoneal covering of viscera.3. Irritation (chemical irritation by HCI in peptic ulcer).4. Overdistension of a hollow viscus e.g urinary bladder.5. Spasm of a hollow viscus e.g gut, gall bladder orureter.Both 4 & 5: Obliteration of blood vesssels ® Ischaemicpain.
Characters of visceral pain1. Dull aching or rhythmic cramps.2. Diffuse (poorly localized).3. Depressor autonomic changes: decreased heart rate, decreasedarterial blood pressure ,nausea & vomiting.4. Rigidity of the overlying muscles.Limitation of the spread of infection.Decrease the mobility of the diseased viscus for relief of pain.5. Referred to the surface area i.e referred pain.
VISCERAL PAIN• Arises from Visceral Organs• Receptors– Free Nerve Endings of A Delta & C Fibers– Sparsely Distributed• Stimulus: Spasm, Distension, Ischemia, Chemical• Ischemia– Release Acid Metabolites– Tissue Degeneration Products Produce Bradykinin &Proteolytic Enzymes• Chemicals– Release of Proteolytic Acid Gastric Juice
VISCERAL PAIN• Input to CNS via Autonomic Nerves• Cell Bodies of Ist Order Neuron– DRG & Homologous Cranial Nerve Ganglia of VII,IX , X & Trigeminal Nerve• Afferent also Enters via Sympathetic Ganglia forReflex Control of Visceral Functions
VISCERAL PAIN• In CNS Fibers Follow Same Route as that of OtherPain Fibers– Poorly Localized, Unpleasant– Associated with Autonomic Changes & Nausea– Usually Referred to Superficial Parts of Body• REFERRED PAIN– Visceral Pain Usually Referred– Deep Pain May Also be Referred
Referred painDefinitionPain originating from viscera but felt in somaticstructures which supplied by the same spinal dorsalroot ( the same dermatome) of the diseased viscus.
Referred pain• Examples• 1. Cardiac pain: is felt in left shoulder.• 2. Gall bladder pain: is felt in tip of right shoulder.• 3. Appendicular pain: is felt around the umbilicus.• 4. Gastric pain: is felt between the umbilicus & xiphoidprocess.• 5. Renal pain: is felt in the back, inguinal region &testicles.• 6. Teeth pain: referred to other teeth.
REFERRED PAIN• Superficial Pain Never Referred• Visceral Pain - Local & Referred– May also Radiate to Distant Site– Cardiac Pain• Inner Aspect of Left Arm, Right Arm, even to Neck &Abdomen– Distension of Ureter• Pain in Testicles– Irritation of Parietal Plura & Peritoneum• Pain Referred to Overlying Surface of Body– Of Diaphragm• Tip of Shoulder
REFERRED PAIN• Mechanism– Dermatome Rule• Parts Develop from Same Embryonic Segment orDermatome• Diaphragm Migrate from Neck• Heart & Arm have Same Segmental Origin• Convergence– Somatic and Visceral Pain Afferents Converge onSame Second Order Neuron– Brain Unable to Differentiate Site of Origin• Hence Pain Felt at Somatic Sites
Mechanism of referred paina. Convergence – projection theoryAfferent pain fibers from the skin and viscousconverge on the same cells of SGR or thalamusand will finally activate the same corticalneurons. Whatever the source of pain, thecortex will project it to the skin beingthe commnest source of pain.
b. Facilitation theoryAfferents of diseased viscera, givefacilitation to cutaneouspain cells in Substantia Gelatinosa ofRolandi (SGR),Which leads to facilitation of theirstimulation.
REFERRED PAIN• Facilitation Effect:– ↑ Activity in Visceral Pain Afferents Collaterals Fibers→ EPSP in Spinal Neurons Receiving Somatic Inputs→ ↑ Activity in Somatic Neurons → Continuous Pain
PAIN• Intensity of Pain is Proportional to Degree ofTissue Damage• Ischemic Pain → Lactic Acid → Nerve EndingStimulation• Muscle Spasm Mechanoreceptor StimulationIschemia• Transmission of Pain– A – Delta Fibers: 6 to 30 M/Sec– C – Fibers: 0.5 to 2 M/Sec
PAIN• Mixed Spinal Nerve• Dorsal Root Ganglia Dorsal Root DorsalHorn• A – Delta Fibers– Terminate in Lamina I of Dorsal Horn Gray Matter (FastPain)Give Local Collateral Branch for Spinal Reflexes• Second Order Neuron– Cross to Opposite Side– Form Anterior Spino-Thalamic Tract (NeospinothalamicTract)• Joins Medial Laminiscus → Few Collaterals to R.F.
PAIN• Second Order Neuron ThalamusPost Central Gyrus• Localization is Good• Neurotransmitter is Glutamate• Few Fibers Ascends in Dorsal Column• Slow pain: C –Fibers Ist Order NeuronLamina II and III
PAIN• Substantia Gelatinosa of Rolando• Interneuron Lamina V Second OrderNeuron Cross → Lateral Spinothalamic Tract• (Paliospinothalamic Tract → Brain Stem Joins →Medial Leminiscus → Thalamus → Cortex
Pain• Brain Stem: Collaterals Given to:– Reticular Formation at All Levels of Brain Stem– Hypothalamus– Peri Ventricular Gray Matter– Peri Aqueduct Gray Matter– Most Fibers End in Intralaminar and Reticular Nucleiof Thalamus– Non Specific Thalamo Cortical Projections to All Partof Cerebral Cortex– To Somato Sensory Cortex SI and SII
PAIN• While Entering Spinal Cord– Fibers Ascends or Descends Few Segments → EntersSpinal Cord• Through Many Inter-Neurons– Information Relayed to Anterior Horn Cells of Same &Opposite Side for Local & Segmental Reflexes ofSpinal Cord
PAIN• Pain & Other Crude Sensations– Perceived Even in Absence of Cerebral Cortex• Cortex is Concerned With– Discriminative, Exact & Meaningful Interpretation of Pain– Emotional Components of Pain• Post Injury Pain– Irritation of Nerve Endings• Allodynia– Minor Touch Causes Pain• Neuropathic Pain– Occur at Sites Even after Healing of Injury– Often Resistant to Analgesics
PAIN• Mechanism– Release of Sensitizing Substance– ↑ Transmission at Synaptic Junctions– At Finer Level• ↑ Activity of Pre-Synaptic NMDA Receptors of PrimaryNerve Ending → ↑ Release of Substance P– Gene Switch• Sub Population of A-Beta Fibers from MechanoreceptorsInputs Start Producing Substance P• NMDA(N-methyl-D-aspartate)– Ion Channels Allow Entry of Ca++
Pain Control Mechanisms• Peripheral• Gating Theory– Involves Inhibitory Inter-Neuron in Cordimpacting NociceptiveProjection Neurons• Inhibited by C Fibers• Stimulated by AAlpha &Beta Fibers• TENS• Central• Direct Electrical + tobrain → Analgesia• Nociceptive controlPathways Descend toCord• Endogenous Opioids
Pain Modulation• Examples– Stress Analgesia– War Situation When Person Emotionally Charged– Pain Relieved by• Acupressure & Acupuncture and Electrical Vibrator• Gate Control Mechanism– Proposed by Malzek & Wall
Pain Control Systems(I) Analgesic systema) The neurons of the periaqueductal gray area are stimulated byB endorphin reaching them from hypothalamus (neurons ofperiventricular area) or pituitary (through blood).b) Fibres of periaqueductal and interneurones of sp.cd. Secrete(Enkephalin)c) Fibres of raphe magnus nucleus secrete (Serotonin)d) Inhibitory interneurones in spinal cord secrete (Enkephalin).
PAIN• DESCENDING PAIN INHIBITING SYSTEM:• Fibers Arise from: Peri-Aqueductal Gray matterPeri-Ventricular Gray MatterHypothalamusMedial Forebrain BundleNeurons around IIIrd & IV ventricleNucleus Reticularis in MedullaSpinal Cord Nucleus RapheMagnusEncephalins
PAIN• Nucleus Raphe Magnus• Dorsal Horn of Spinal Cord in SubstantiaGelatinosa• Pre-Synaptic and Direct Inhibition by Blocking Ca++ Channels• Blocking of Pain SignalsSerotonergicNeurons
• Natural Opioids-Endorphins•released from their storageareas in the brain when apain impulse reaches thebrain,• bind to receptors in thepain pathway to blocktransmission and perceptionof pain.
(II) Brain Opiate SystemOpiate receptors in the brain cause pre and postsynapticinhibition of the nociceptive pathway.Sites of opiate receptors1. Periaqueductal gray area2. Periventricular aea.3. Raphe magnus nucleus in medulla.4. Substantia nigra.
Opioid peptides(1) Enkephalins.Act as neurotransmitters at the analgesic system.(2) Endorphins-In hypothalamus act as neurotransmitters.-In pituitary act as hormone.Release during stress leading to stress analgesia.(3) DynorphinVery potent analgesic.Types of opiate receptorsDelta, Mu, Kappa, Sigma & Epislon.
BRAIN OPIOID SYSTEM• Opium– Alkaloid– Morphine Derived from Opium → Analgesia– Receptors are Opioid Receptors• Found in Many Areas of Brain– Limbic System Hypothalamus, Peri-Ventricular Areas, Pituitary &Spinal Cord• Endogenous Substances which Mimic Action ofOpium → Opioid Peptides– Brain’s Own Morphine– Act like Neurotransmitter on Opioid Receptors
BRAIN OPIOID SYSTEM• Opioid Peptides– Beta Endorphins• Derived from Pro-opiomelanocortin– Met-and Leu-Encephalins• Derived from-Proencephalins– Dynorphin– Derived from Prodynorphin• Opioid Peptides Cause Pre-synaptic Inhibition– At Spinal Cord to Block Pain• Inhibit Release of Substance P
BRAIN OPIOID SYSTEM• Cause Post Synaptic Inhibition– Produce IPSP• In Limbic Areas & Hypothalamus– Pain Modulation• Act Peripherally at Site of Injury• Opioid Mediated Endogenous Analgesia System→ Activated by Administration of ExogenousMorphine• Descending Analgesia System– Under Tonic Inhibitory Control of Mid Brain &Medulla– Opiates Inhibit these Inhibitory Inter-Neurons
(III) Gate theory1) Spinal gate:SGR (substantia gelatinosa of Rolandi) in layers II & III acts as gate. Atthis level, there is a group of inhibitory enkephalinergic interneuronswhich form the "Pain Inhibitory complex, PIC". When stimulated,these interneurons block the transmission of painsensation by presynaptic inhibition of pain-conducting fibers.
This gate can be closed by:Impulses from1. A beta fibres: (rubbing of skin inhibits pain).2. A delta fibres; counter irritant and acupuncture inhibitpain. They stimulate cutaneous receptors which sendimpulses through A delta fibres stimulate the PIC.3. Cortico-fugal fibres: (thinking decrease pain).All these fibers causes presynaptic inhibition of pain byactivating an interneurone which secrete (GABA).
2)Thalamic gate:The same "gating" mechanism for pain is found also at thethalamus wherepain signals could be blocked by corticofugal fibers orfacilitated byintralaminar thalamic nuclei. In this way,the thalamus considered as a secondary gate far paintransmission.
Stress analgesia; During stress, Pain is blocked attwo levels :A) At the thalamus: (the second gate of pain transmission ).Corticofugal fibers to the thalamus block by presynaptic inhibition thetransmission of pain signals in the thalamus before they reach the cerebral cortex.B) At the dorsal horn of the spinal cord: (the first gate of paintransmission).The hypothalamus, and other parts of the central analgesia system, activate thespinal PIC which blocks the transmission of pain signals at the dorsal horn.
Melzack and Wall (1965, 1988) developed a comprehensivetheory of pain (‘gate-control theory’) which has generallyreceived wide support• Fast ‘touch’ fibres and slow ‘pain’ fibresconnect with substantia gelatinosa (SG) and transmission cells (Tcells) in spinal cord• T cells send pain information to the brain• SG acts as “gate” to allow or inhibit T cells
GATE CONTROL MECHANISMS.G.CellsT- CellsType II FibersA-DELTA &C Fibers(-)(-)(+)(-)(+)SpinoThalamicPathway(-)
Activity in fast fibers tends to close the gate (touch butno pain) and slow fibers open the gate (pain)A light touch accompanying a noxious stimulus partially closesgate (reduces pain) — rub skin to alleviate painPsychological factors? Modify gate via descending pathwayand/or release of endogenous opiates (e.g. endorphins) in the CNSproducing analgesic effects.Ignore pain to escape from greater danger (e.g. death!)
Headache• Brain is insensitive to pain.• Pain sensitive intracranial structure;• (Arteries, Veins, Nerves and Dura at the base ofthe brain)• Headache is referred pain• a. Supratenterial is referred along theophthalmic n ® frontal Head ache.• b. Infratentorial is referred along Cervical 2 ®occipital Headache.
Causes of intracranial headache: 5%1. Meningeal irritation; me nin gitis ; gen eral ize d.Br ain tum our; loca lize d.2. Migraine headache; Abn orma l va scul ar phe nom enon.3. Hypertension: He ada che a pu lse Pre ssur e.4. Low CSF pressure: Rem oval of 20 ml of CS F.® bra in desc ent ® tra ctio n of th e d ura & h ead ache .5. Alcoholic headacheal coh ol pr odu ces dir ect meni nge al irrita tio n.6. Constipation.Ab sorp tion of tox ins pro duce s di rect me nin geal irritati on.
Causes of intracranial headache: 5%• 1. Meningeal irritation; meningitis ; generalized.• Brain tumour; localized.• 2. Migraine headache; Abnorma l vascular phenomenon.• 3. Hypertension: Headache a pulse Pressure.• 4. Low CSF pressure: Removal of 20 ml of CSF.• ® brain descent ® traction of the dura & headache .• 5. Alcoholic headache• alcohol produces direct meningeal irritation.• 6. Constipation.• Absorption of toxins produces direct meningeal irri tation.
Causes of extra-cranial headache95%• 1. Muscular spasm of scalp and neckmuscles due to emotions .• 2. Irritation of the nasal sinuses.• 3. Errors of refraction .• 4. Otitis media.• 5. Toothache.
Hyperalgia(increased painsensation)• 1. primary hyperalgesia;• It occurs in the inflammed skin due todecreased threshold of pain receptors• by bradykinin, K, Histamine andprostaglandins.• So non painful stimuli become painful.
HyperalgiaSecondary hyperalgesia;It occurs in normal skin due to increasedthreshold of pain receptors. So pain receptorsneed stronger stimulus, but once pain is elicited ,it isvery severeIt can be explained by (Convergence facilitationtheory).Impulses from the injured area facilitate a centralneuron. Impulses from the area ofsecondary hyperalgesia converge on same centralneuron. The convergence on a centralfacilitated neuron explains the exaggerated painsensibility.
Why the threshold of pain is increased in the area of secondaryhyperalgesia.The facilitator neuron which arises from the area of primaryhyperalgesia exerts lateral inhibition on the stimulator neuronwhich arises from the area of secondary hyperalgesia.