pain sensations

Pain sensations

Dr Raghuveer Choudhary

PAIN

• An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. – (International association for the study of pain

1979)

Damaged tissues release proteolytic enzymes, K+ &histamine .Proteolytic enzymes act on globulins in the interstitial Fluid to release kinins.e.g bradykinin, K+ and histamine stimulate pain receptorsPain is a protective sensation.

Pain receptors . Free nerve endingsThree types1. Mechanical pain Receptors.: stimulated by mechanical injurious stimuli.2. Thermal pain Receptors. : discussed before.3. Chemical pain Receptors.: stimulated by chemical stimuli.Chemical stimuli include:bradykinin (most important) serotonin, histamine & K+.

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 nonadaptive receptors.

Types of pain Pain 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 is transmitted through peripheral nerves to the spinal cord and from there to the brain. This happens through two different types of nerves fibers:

• 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 as sharp.

• “slow pain”, more a dull and burning. • Occurs after a short time• lasts a few days or weeks,• Chronic pain-if inappropriately processed by

the body, it can last several months

Fast pain

• nerves are called A-delta fibers. • relatively thick size nerve fibers allow the pain

stimulus to be transferred very fast (at a speed of five to 30 meter/second), hence the name

• This is all to make the body withdraw immediately from the painful and harmful stimulus, in order to avoid further damage.

Slow Pain

• starts immediately after the fast pain• is transmitted by very thin nerve fibers, called

C-nerve fibers (their diameter is between 0.2 to 1 thousandth of a millimeter).

• pain impulse can only be transmitted slowly to the brain, at a speed of less than 2 meters per second.

• Body response -immobilization (guarding, spasm or rigidity), so that healing can take place.

(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, aching throbbing nauseous)

After one second .Prolonged;annoying,intolerable.Elicited by All types of R.C fibresEnds in non specific thalamic nuclei & 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 VB

Complex of Thalamus

• Slow• C Fibers• Substance P• Paleospinothalamic• Polymodal/Chemical• Poor Localization• Dull, Burning, Aching• Terminate; RF– Tectal Area of Mesen.– Periaqueductal Gray

Nociceptive Pathways

• Spinothalamic - Major – Neo- Fast (A Delta)– Paleo- Slow (C Fibers)

• Spinoreticular• Spinomesencephalic• Spinocervical (Mostly Tactile)• Dorsal Columns (Mostly Tactile)

PAIN

• A-DELTA→ Noxious Stimulation → change in Membrane Potential → Receptor Potential → A. P.

• C-FIBERS: Damaged Cell → Proteolytic Enzymes

Circulating Gamma Globulins

Bradykinin, Substance P

Stimulation of Nerve Ending

Fast pain is transmitted by A delta fibers (5-15 m/sec.) from skin(mainly), parietal pleura, peritoneum a & Synovial membrane.

(1) Somatic (motor) reflexes:- Spinal reflexes.Flexor withdrawal reflex.(2) Autonomic reactions:-Cutaneous pain: Pressor effects (increased heart rate & ABP).DEEP & visceral pain: Depressor effects (decreased heart rate & ABP).(3) Emotional reactions:--Acute pain: Crying and anxiety.(4) Hyperalgesia:- mainly due to skin lesion. (increased pain sensibility).

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-laminar nuclei) and reticular formation have a strong arousal effect on the brain which prevents sleep during pain.

Deep pain C. FibresDiffuse, Dull aching and Depressor effects.Causes: - inflammation, ischaemia or muscle spasm.- Bone fractures; due to stimulation of periosteal pain receptors.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 Blood

Pressure

• Often Nauseating

• Transmitted via Antero Lateral System

Ischaemic painType of deep pain felt in muscles when their blood supply is decreased.The Patients complains of severe pain in the muscles upon walking or running due to accumulation of pain producing 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 or ureter.Both 4 & 5: Obliteration of blood vesssels ® Ischaemic pain.

Characters of visceral pain1. Dull aching or rhythmic cramps.2. Diffuse (poorly localized).3. Depressor autonomic changes: decreased heart rate, decreased arterial 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 for

Reflex Control of Visceral Functions

VISCERAL PAIN

• In CNS Fibers Follow Same Route as that of Other

Pain 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 somatic structures which supplied by the same spinal dorsal root ( 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 & xiphoid

process.• 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

REFERRED PAIN• Mechanism – Dermatome Rule• Parts Develop from Same Embryonic Segment or

Dermatome• Diaphragm Migrate from Neck• Heart & Arm have Same Segmental Origin

• Convergence– Somatic and Visceral Pain Afferents Converge on

Same 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, give facilitation to cutaneouspain cells in Substantia Gelatinosa of Rolandi (SGR),Which leads to facilitation of their stimulation.

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 of Tissue Damage

• Ischemic Pain → Lactic Acid → Nerve Ending Stimulation

• Muscle Spasm Mechanoreceptor Stimulation

Ischemia• 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 Dorsal Horn• A – Delta Fibers– Terminate in Lamina I of Dorsal Horn Gray Matter (Fast

Pain)Give Local Collateral Branch for Spinal Reflexes

• Second Order Neuron– Cross to Opposite Side– Form Anterior Spino-Thalamic Tract (Neospinothalamic Tract)

• Joins Medial Laminiscus → Few Collaterals to R.F.

PAIN

• Second Order Neuron Thalamus

Post Central Gyrus

• Localization is Good• Neurotransmitter is Glutamate• Few Fibers Ascends in Dorsal Column• Slow pain: C –Fibers Ist Order Neuron

Lamina II and III

PAIN

• Substantia Gelatinosa of Rolando

• Interneuron Lamina V Second Order Neuron 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 Nuclei

of Thalamus– Non Specific Thalamo Cortical Projections to All Part

of Cerebral Cortex– To Somato Sensory Cortex SI and SII

PAIN

• While Entering Spinal Cord

– Fibers Ascends or Descends Few Segments → Enters

Spinal Cord

• Through Many Inter-Neurons

– Information Relayed to Anterior Horn Cells of Same &

Opposite Side for Local & Segmental Reflexes of

Spinal 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 Primary

Nerve Ending → ↑ Release of Substance P

– Gene Switch• Sub Population of A-Beta Fibers from Mechanoreceptors

Inputs 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 Cord impacting Nociceptive Projection Neurons• Inhibited by C Fibers• Stimulated by A Alpha &

Beta Fibers• TENS

• Central• Direct Electrical + to

brain → Analgesia• Nociceptive control

Pathways Descend to Cord

• 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 by B endorphin reaching them from hypothalamus (neurons of periventricular 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 matter Peri-Ventricular Gray Matter Hypothalamus Medial Forebrain Bundle Neurons around IIIrd & IV ventricle

Nucleus Reticularis in MedullaSpinal Cord Nucleus Raphe Magnus

Encephalins

PAIN

• Nucleus Raphe Magnus

• Dorsal Horn of Spinal Cord in Substantia Gelatinosa

• Pre-Synaptic and Direct Inhibition by Blocking Ca ++ Channels

• Blocking of Pain Signals

Serotonergic Neurons

• Natural Opioids-Endorphins

•released from their storage areas in the brain when a pain impulse reaches the brain,

• bind to receptors in the pain pathway to block transmission and perception of pain.

• opioid pain inhibition at multiple levels– spinal cord– brain-stem– thalamus

(II) Brain Opiate System

Opiate receptors in the brain cause pre and postsynaptic inhibition 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 of Opium → 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 Exogenous Morphine

• 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. At this level, there is a group of inhibitory enkephalinergic interneurons which 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 inhibit pain. They stimulate cutaneous receptors which send impulses through A delta fibres stimulate the PIC.3. Cortico-fugal fibres: (thinking decrease pain).All these fibers causes presynaptic inhibition of pain by activating an interneurone which secrete (GABA).

2)Thalamic gate:The same "gating" mechanism for pain is found also at the thalamus wherepain signals could be blocked by corticofugal fibers or facilitated byintralaminar thalamic nuclei. In this way,the thalamus considered as a secondary gate far pain transmission.

Stress analgesia; During stress, Pain is blocked at two 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 pain transmission).The hypothalamus, and other parts of the central analgesia system, activate the spinal PIC which blocks the transmission of pain signals at the dorsal horn.

Melzack and Wall (1965, 1988) developed a comprehensive theory of pain (‘gate-control theory’) which has generally received wide support

• Fast ‘touch’ fibres and slow ‘pain’ fibresconnect with substantia gelatinosa (SG) and transmission cells (T cells) in spinal cord• T cells send pain information to the brain• SG acts as “gate” to allow or inhibit T cells

GATE CONTROL MECHANISM

S.G.CellsT- Cells

Type II Fibers

A-DELTA & C Fibers

(-)

(-)(+)

(-)(+)

SpinoThalamicPathway

(-)

Activity in fast fibers tends to close the gate (touch but no pain) and slow fibers open the gate (pain)

A light touch accompanying a noxious stimulus partially closesgate (reduces pain) — rub skin to alleviate pain

Psychological 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 of

the brain)• Headache is referred pain• a. Supratenterial is referred along the

ophthalmic 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 eno n.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 irri tati 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 headache 95%

• 1. Muscular spasm of scalp and neck muscles due to emotions .

• 2. Irritation of the nasal sinuses.• 3. Errors of refraction .• 4. Otitis media.• 5. Toothache.

Hyperalgia(increased pain sensation)

• 1. primary hyperalgesia;• It occurs in the inflammed skin due to

decreased threshold of pain receptors• by bradykinin, K, Histamine and

prostaglandins.• So non painful stimuli become painful.

HyperalgiaSecondary hyperalgesia; It occurs in normal skin due to increased threshold of pain receptors. So pain receptors need stronger stimulus, but once pain is elicited ,it is very

severe It can be explained by (Convergence facilitation theory). Impulses from the injured area facilitate a central neuron.

Impulses from the area of secondary hyperalgesia converge on same central neuron.

The convergence on a central facilitated neuron explains the exaggerated pain

sensibility.

Why the threshold of pain is increased in the area of secondary hyperalgesia.The facilitator neuron which arises from the area of primary hyperalgesia exerts lateral inhibition on the stimulator neuron which arises from the area of secondary hyperalgesia.