pain

1. Pain:- Pain pathway, aetiology and types of pain.

2. Objectives
1.To understand the complete neuroanatomical and physiological basis of pain perception as explained in Davidson,
including peripheral and central processing.
2.To study how nociceptors convert noxious stimuli into electrical signals through transduction and transmission
mechanisms.
3.To learn the detailed ascending pathways involved in pain conduction such as spinothalamic, spinoreticular, and
trigeminothalamic tracts.
4.To classify pain into nociceptive, neuropathic, inflammatory, psychogenic, somatic, and visceral categories, with
clinical examples.
5.To understand etiological factors contributing to acute and chronic pain, including metabolic, inflammatory,
ischemic, and neurological causes.
6.To integrate anatomical knowledge with clinical application for accurate diagnosis and management of pain
disorders.

3. Introduction to Pain
1.Pain is defined in Davidson as a complex sensory and emotional experience that arises when actual or potential
tissue damage occurs, involving both peripheral tissue signals and higher brain interpretation.
2.Pain perception is influenced by cognitive, emotional, and cultural factors, meaning that two individuals with the
same injury may experience pain differently.
3.Pain consists of a sensory-discriminative component (localization, intensity, quality) and an affective-emotional
component (suffering, distress).
4.Acute pain acts as a protective mechanism, alerting the body to damage, while chronic pain loses its protective
value and becomes a pathological condition.
5.Davidson emphasizes pain as one of the most frequent presenting complaints in clinical practice, requiring a
systematic approach to identify underlying causes.
6.A complete assessment includes onset, duration, radiation, aggravating/relieving factors, associated symptoms,
and functional impact on daily activities.

4. 3 – Anatomy of Nociceptors
1.Nociceptors are specialized peripheral sensory receptors located in skin, fascia, viscera, muscles, and blood
vessels, responding only when stimuli exceed a threshold capable of causing tissue damage.
2.A-delta fibres are thinly myelinated fibres responsible for sharp, well-localized pain; they respond rapidly to
mechanical and thermal stimuli.
3.C-fibres are unmyelinated, slow-conducting fibres responsible for dull, burning, aching pain, forming the basis of
chronic and poorly localized pain.
4.Nociceptors become activated by mechanical injury, extreme temperature, or chemical mediators (prostaglandins,
serotonin, bradykinin).
5.During inflammation, nociceptors undergo peripheral sensitization, resulting in exaggerated pain responses such
as hyperalgesia and allodynia.
6.Nociceptive signalling is the first step in pain conduction, and abnormalities here contribute to conditions like
fibromyalgia and complex regional pain syndrome.

5. Overview of Pain Pathway
1.Pain processing involves four major steps: transduction (stimulus to nerve signal), transmission (nerve signal to
spinal cord and brain), modulation (inhibition or amplification), and perception (interpretation in cortex).
2.Peripheral injury activates nociceptors, which convert mechanical or chemical stimuli into electrical impulses
through ion-channel opening.
3.Electrical signals travel via peripheral nerves toward the dorsal root ganglion and enter the spinal cord through the
dorsal horn.
4.Within the spinal cord, pain signals synapse in specific laminae before ascending through major pathways.
5.Pain impulses reach the thalamus, the central relay station, where crude localization occurs.
6.Final interpretation occurs in the somatosensory cortex, where the brain identifies location, severity, and
emotional relevance.

6. First-Order Neurons
1.First-order neurons begin at nociceptor terminals and their cell bodies reside in the dorsal root ganglion,
representing the first link in the pain pathway.
2.A-delta fibres transmit fast, sharp pain and synapse mainly in lamina I and V, while C-fibres transmit slow, dull pain
and synapse predominantly in lamina II (substantia gelatinosa).
3.Pain neurotransmission depends on key excitatory neurotransmitters, mainly glutamate (fast synaptic
transmission) and substance P (slow, prolonged transmission).
4.The intensity of pain depends on the frequency of action potentials generated at the nociceptor level.
5.Peripheral nerve injury may cause ectopic impulse generation, contributing to neuropathic pain syndromes.
6.First-order neuron injury leads to conditions like peripheral neuropathy, post-herpetic neuralgia, or compressive
radiculopathies.

7. Second-Order Neurons
1.Second-order neurons are located in the dorsal horn and receive synaptic input from first-order nociceptive fibres.
2.These neurons cross to the opposite side of the spinal cord through the anterior white commissure within 1–2
spinal segments of entry.
3.They ascend via the spinothalamic tract, the most important pathway for pain and temperature conduction.
4.Subdivisions: the lateral spinothalamic tract (sharp, localized pain) and the anterior spinothalamic tract (dull,
poorly localized pain).
5.These neurons project to the ventral posterolateral (VPL) nucleus of the thalamus.
6.Damage to the spinothalamic tract results in contralateral loss of pain and temperature sensation below the
lesion.

8. Third-Order Neurons
1.Third-order neurons originate in the thalamic VPL nucleus and send projections to the primary somatosensory cortex
(postcentral gyrus).
2.These neurons are responsible for the conscious perception of pain—allowing the brain to identify the precise location and
intensity of the stimulus.
3.Parallel projections to limbic structures such as the anterior cingulate cortex and amygdala generate the emotional component
of pain.
4.Signals also travel to the insular cortex, integrating pain with autonomic and homeostatic responses.
5.Thalamic lesions (e.g., thalamic stroke) can produce severe central pain syndromes characterized by burning, intractable pain.
6.Higher centres integrate memory, emotion, attention, and past experiences to shape pain perception.

9. Pain Modulation (Descending Pathways)
1.Pain signals can be either amplified or inhibited by descending brain pathways originating from the periaqueductal
grey (PAG) in the midbrain.
2.PAG receives input from the cortex and limbic system, allowing emotional states to influence pain intensity.
3.Descending fibres travel to the nucleus raphe magnus and locus coeruleus, releasing serotonin and
norepinephrine, which inhibit dorsal horn pain neurons.
4.Endogenous opioids (endorphins, enkephalins) bind to opioid receptors and reduce neurotransmitter release from
nociceptors.
5.Effective modulation prevents exaggerated pain responses; dysfunction contributes to chronic pain, fibromyalgia,
and neuropathic pain.
6.Many modern analgesic treatments (e.g., antidepressants, opioids) act by enhancing descending inhibition.

10. Gate Control Theory
1.The Gate Control Theory describes how non-painful stimuli (e.g., touch) modulate pain signals at the spinal cord
level through inhibitory interneurons.
2.Large-diameter A-beta fibres activated by touch, vibration, or pressure inhibit transmission of pain signals carried
by A-delta and C fibres.
3.Psychological factors such as attention, anxiety, and mood influence the “gate,” either closing (reducing pain) or
opening (exaggerating pain) it.
4.This theory explains why rubbing or applying pressure to a painful area provides relief.
5.It forms the basis for treatments like TENS, physiotherapy, and acupuncture, which stimulate non-nociceptive
fibres.
6.Malfunctioning of the gating mechanism contributes to chronic pain syndromes and central sensitization.

11. Aetiology of Pain
1.Tissue injury from trauma, inflammation, or infection stimulates nociceptors directly and releases inflammatory mediators
causing pain.
2.Ischemic pain, seen in myocardial infarction or peripheral arterial disease, results from inadequate blood flow leading to
metabolite accumulation.
3.Neuropathic causes include nerve compression, demyelination, metabolic neuropathies, or infection causing burning or electric
shock–like pain.
4.Referred pain occurs when visceral afferents converge on the same spinal segments as somatic nerves, producing pain at
distant sites.
5.Psychological factors such as depression or anxiety intensify pain perception by altering central modulation pathways.
6.Metabolic causes like diabetes, uremia, alcoholism, or vitamin B12 deficiency lead to chronic neuropathy-related pain.

12. Nociceptive Pain
1.Caused by activation of nociceptors due to tissue damage or inflammation, forming the majority of
acute pain syndromes.
2.It is subdivided into somatic and visceral pain, each having distinct pathways and clinical features.
3.Somatic nociceptive pain is usually sharp and localized, while visceral pain is deep, dull, and poorly
localized.
4.Pain acts as a protective mechanism, alerting the body to potential or actual harm.
5.Persistent stimulation may cause peripheral and central sensitization, contributing to chronic pain.

13. Somatic Pain
1.Originates from skin, muscles, joints, bones, and connective tissue, which contain abundant nociceptors
allowing precise localization.
2.Sharp, stabbing, or throbbing in nature, indicating involvement of A-delta fibres in acute injury.
3.Common causes: fractures, sprains, arthritis, myalgia, soft tissue injuries.
4.Pain worsens with movement and improves with rest or immobilization.
5.Inflammatory mediators increase peripheral sensitization, making the area tender on palpation.
6.Management includes NSAIDs, rest, immobilization, physiotherapy, and treating underlying
inflammatory or mechanical causes.

14. Visceral Pain
1.Generated from internal organs, which have sparse nociceptors leading to diffuse, poorly localized pain.
2.Often associated with autonomic symptoms such as nausea, sweating, vomiting, and changes in blood pressure.
3.Mechanisms include organ distension, ischemia, inflammation, and traction on mesentery.
4.Visceral pain frequently presents as referred pain due to shared spinal segment innervation (e.g., gallbladder →
right shoulder).
5.Classic examples include renal colic, biliary colic, pancreatitis, appendicitis, and intestinal obstruction.
6.Requires addressing underlying pathology; analgesics may provide partial relief but diagnostic accuracy is crucial.

15. Neuropathic Pain
1.Arises from pathological changes in peripheral or central nerves rather than from tissue injury.
2.Characteristic symptoms include burning, electric shock–like sensations, tingling, numbness, and shooting pains.
3.Allodynia (pain from normally non-painful stimuli) and hyperalgesia (excessive pain response) are hallmark
features.
4.Common causes: diabetic neuropathy, post-herpetic neuralgia, trigeminal neuralgia, chemotherapy-induced
neuropathy.
5.NSAIDs and opioids offer limited relief because nociceptors are not the primary source of pain.
6.Davidson recommends anticonvulsants (gabapentin, pregabalin), antidepressants (amitriptyline), and nerve
blocks.

16. Central Pain
1.Results from injury or disease of the brain or spinal cord, leading to abnormal processing of pain signals.
2.Seen in conditions like stroke (especially thalamic lesions), multiple sclerosis, and spinal cord injuries.
3.Pain is often severe, constant, and burning, frequently resistant to standard analgesics.
4.Mechanism involves damage to central pathways, leading to spontaneous neuronal firing and altered inhibitory
control.
5.Emotional distress, depression, and anxiety worsen the intensity and impact of central pain.
6.Treatment requires multimodal therapy: antidepressants, anticonvulsants, psychological support, and
somatosensory rehabilitation.

17. Referred Pain
1.Pain felt in a location away from the actual site of pathology due to convergence of visceral and somatic afferents on the same
spinal cord segments.
2.The brain misinterprets visceral pain as originating from a somatic region with more frequent sensory input.
3.Examples:
– Myocardial ischemia → chest, left arm, jaw
– Gallbladder inflammation → right shoulder/scapula
– Renal colic → groin or inner thigh
4.Referred pain patterns are consistent and aid in diagnosis during bedside clinical examination.
5.Referred pain is usually deep, dull, and poorly localized.
6.Treatment depends on identifying and correcting the underlying visceral pathology.

18. Inflammatory Pain
1.Caused by activation of nociceptors due to inflammatory mediators like prostaglandins, cytokines, and histamine
released during tissue injury.
2.Characterized by warmth, redness, swelling, tenderness, and loss of function, summarized by cardinal signs of
inflammation.
3.Inflammation activates both nociceptive fibres and immune pathways, increasing pain severity.
4.Chronic inflammatory conditions such as rheumatoid arthritis lead to persistent sensitization and chronic pain.
5.Pain improves with anti-inflammatory medications, cold packs, rest, and treating the primary inflammatory
condition.
6.Inflammatory pain bridges nociceptive and neuropathic mechanisms as long-standing inflammation can damage
nerves.

19. Psychogenic & Functional Pain
1.Pain significantly influenced or exaggerated by psychological factors without proportionate physical
findings.
2.Emotional stress, anxiety, depression, traumatic experiences, and catastrophizing amplify pain signals.
3.Brain imaging studies show altered pain modulation and increased limbic system activation in functional
pain disorders.
4.Seen in conditions like somatoform disorders, fibromyalgia, tension headaches, and chronic widespread
pain.
5.Management includes cognitive-behavioural therapy, antidepressants, relaxation techniques, and
reassurance.
6.Davidson stresses not dismissing psychogenic pain as “imaginary”—the pain is real, but mechanisms are
central.

20. Chronic Pain Mechanisms
1.Defined as pain persisting beyond normal healing time (>3 months), losing its protective purpose.
2.Central sensitization leads to heightened pain perception due to increased excitability of spinal
neurons.
3.Long-term changes include altered neurotransmitter levels, synaptic plasticity, and reduced inhibitory
control.
4.Psychological factors such as fear, stress, and depression maintain chronic pain cycles.
5.Chronic pain frequently coexists with sleep disturbances, fatigue, loss of function, and reduced quality
of life.
6.Effective management requires a multimodal approach: pharmacotherapy, physiotherapy,
psychological support, and lifestyle modifications.

21. Conclusion
1.Pain is a multidimensional phenomenon involving complex interactions between peripheral tissues, spinal
pathways, and higher brain centres.
2.Understanding the pain pathway helps clinicians identify the source, mechanism, and most appropriate
treatments.
3.Aetiology includes nociceptive, neuropathic, ischemic, inflammatory, metabolic, and psychogenic causes, each
requiring tailored management.
4.Davidson emphasizes the importance of evaluating pain location, quality, severity, associated symptoms, and
impact on life.
5.Proper classification of pain leads to more accurate diagnosis and effective treatment strategies.
6.A comprehensive approach integrating medical, psychological, and rehabilitative methods provides the best
outcomes for patients.