Understanding Pain: Definition, Significance & Perception

Pain: Definition and Significance

• Pain involves unpleasant sensory and emotional experiences linked to actual or potential tissue damage.
• It serves as a protective mechanism, where activation of nociceptors lead to protective reflexes.
• Pain universally signals potential disease or injury
• It is a dominant symptom prompting patients to seek medical care.
• A primary goal of medicine is to alleviate pain, aiming to restore health and reduce suffering.
• Pain perception: subjective and influenced by developmental, behavioral, personality, and cultural variables.
• Socioeconomic impact: Chronic pain has a huge "massive worldwide” socio-economic impact
• Main Reason: Chronic pain is the main reason people seek medical consultation.
• In the US, chronic pain treatment: Over 2 million people are incapacitated, over 100 million workdays are lost, and >$70 billion is spent annually on medical care.
• Drug Companies: Pain treatment is among the most profitable areas for drug companies.

Classes of Pain

• Fast pain is felt ~0.1 sec after stimulus
• Fast pain presents as sharp and precisely localized sensation
• Fast pain typically is not felt in most visceral tissues
• Slow pain is felt >1 sec after stimulus, increasing over seconds or minutes.
• Slow presents as chronic, aching, or throbbing
• Slow pain found in skin and viscera
• Slow pain persists for a long time, potentially including back pain, tumors, and headaches.

Common Pain Causes

• Infection: Tissue damage from bacteria or viruses can induce pain.
• Heat pain: typically perceived when skin is heated >45°C, which correlates with tissue destruction temperatures.
• Tissue ischemia: Pain arises from lactic acid accumulation during metabolism.
• Tissue ischemia may also come from bradykinin and proteolytic enzymes.
• Muscle spasm is a common pain cause: Can result from direct nociceptor stimulation or compression of blood vessels --> ischemia
• Chemical stimuli: Acidic gastric juice exposure due to ruptures from gastric or duodenal ulcers.
• Headaches: referred pain originating from the cranium or sinuses.
• Headaches commonly involve inflammation of meninges, altered cerebrospinal fluid pressure, or blood vessel issues.
• Overdistension of hollow viscus: pain caused by tissue overstretch or collapsed blood vessels around the viscera.

Nociceptors

• Nociceptors = free sensory nerve endings of myelinated or unmyelinated fibers
• Nociceptive axons include small myelinated Aδ fibers (2-5 μm diameter) & unmyelinated C fibers (0.4-1.2 μm diameter).
• Aδ fibers conduct impulses at 6-30 m/s
• C fibers conduct impulses at 0.5-2 m/s
• Aδ fibers mediate sharp pain
• C fibers mediate slow dull pain
• Nociceptors respond to tissue-damaging stimuli (noxious stimuli)
• Nociceptors found widely in the body with exception of the brain and bones
• Pain receptors adapt slowly or not at all but show central adaptation --> inhibition of centres in the thalamus, reticular formation, lower brain stem and spinal cord
• Aδ and C afferent fibers synapse in the spinal cord
• Glutamate and substance P are the neurotransmitters

Types of Pain Receptors

• Mechanical nociceptors: respond to strong pressure, e.g., sharp objects.
• Thermal nociceptors signal burning heat (>45°C) or cold.
• Chemical nociceptors: react to chemical stimuli like K+, bradykinin, pH extremes, histamine, serotonin and proteolytic enzymes.
• Chemical nociceptors typically stimulate slow pain.

Hyperalgesia and Allodynia

• Hyperalgesia: increased sensitivity to noxious stimuli in damaged tissues and lowered pain threshold.
  • Primary: heightened pain sensitivity within the damaged tissue itself.
  • Secondary: Injured tissue become super-sensitive; manifest in pain ascending pathways
• Allodynia: pain induced by innocuous stimuli.
• Damaged tissues release chemical substances that activate nociceptors, which include K+, H+, bradykinin, prostaglandin, and serotonin from blood and nerve endings.

Mechanisms of Hyperalgesia

• Leaky blood vessels: cause edema and redness.
• Mast cells releasing histamine excite nociceptors.

Ascending Pain Pathways

• Pain sensations travel into the spinal cord and synapse with 2nd-order neurons in the dorsal horn or interneurons for local circuits.
• The 2nd-order neurons ascend to the brain --> contralateral spinothalamic tracts.
• These tracts synapse with 3rd order neurons in the thalamus, which proceed to the postcentral gyrus.
• Pain pathway branches also terminate within the limbic system and hypothalamus.
• Afferent fibres enter the spinal cord, synapsing in laminae II and III at the substantia gelatinosa,
• Substance P = the primary neurotransmitter at the first synapse in the pain pathway, which crosses the midline and ascends via the lateral spinothalamic tract.

Referred Pain

• Referred pain is perceived as coming from an area distant from its actual source.
• Visceral pain is felt in somatic structures elsewhere
• A myocardial infarction may produce pain in the inner aspect of the left arm.
• Irritation of the central portion of the diaphragm can cause pain in the shoulder tip
• Distension of testicles: testicle pain
• Dermatomal rule: Pain is referred to structures that develop from the same embryonic segment or dermatome as origin site.
• Diaphragm referred pain: The diaphragm migrates from the neck down to the chest and abdomen, taking its phrenic nerve.
  • Afferent nerves in the phrenic nerve (1/3 of the nerves) enter spinal cord @ 2nd-4th cervical segments--> site where shoulder tip nerves enter the spinal cord

Dermatome

• Each Spinal nerve contains sensory neurons serving a specific segment
• Dermatome: Area of the skin providing sensory input to the CNS via ONE pair of spinal nerves. Note, adjacent dermatomes often overlap
• Knowing which spinal cord segments feed each dermatome allows us to find damaged regions of Spinal cord

Neuropathic Pain

• Neuropathic pain --> pain that is present even a lack of nociceptor stimulation
• Commonly occurs after damage to peripheral nerves or the CNS regions that transmit pain signals.
• Phantom limb pain = an example of neuropathic pain
• Anterolateral cordotomy = solution to Neuropathic Pain

Gate Theory of Pain Control

• First component: localized in the spinal cord
• Inhibitory neurons link large-diameter mechanoreceptor axons with small-diameter nociceptive axons as they enter the dorsal horn.
• Second component localized in the periaqueductal gray matter
• Mechanoreceptor pathway active = Interneurons inhibit nearby nociceptive pathways and suppress painful info before the signal projects up the spinal cord
• The PAG is the descending pathway that receives signals and sends the message to the dorsal horn of the spinal cord --> depress the nociceptive neurons
• Neurotransmitters in this pathway include: Endorphin, serotonin, enkephalins and serotonin are the neurotransmitters in this pathway

Treatment for Pain

• Opioids (e.g., heroin, codeine) --> Morphine is the most effective
• Pain management techniques: Central inhibition due to endorphins, acupuncture, and rubbing/shaking the injured area to stimulate large-diameter touch pressure afferents, inhibiting pain pathways

Explore the multifaceted nature of pain, its role as a protective mechanism, and its significant socioeconomic impact. This lesson delves into the subjective perception of pain, influenced by various factors, and emphasizes the importance of pain alleviation in medicine. Chronic pain is a primary driver for medical consultations worldwide.