Physiology of pain

• Noxious stimuli are detected by free nerve endings, which can be found anywhere in the body except on the palms of hands and soles of feet.
• The dorsal horn is the site where nociceptive information from the periphery enters the CNS.
• Free nerve endings have no specialized receptors but respond to mechanical or chemical changes in their environment.
• The nociceptor is activated when there is damage to tissues such as inflammation, infection, or trauma.
• Pain signals travel along sensory neurons to the spinal cord and then to the brainstem, thalamus, and somatosensory cortex.
• There are two types of neurons involved in transmitting nociceptive signals to the brain - A-delta fibers (fast) and C fibers (slow).
• A-delta fibers transmit sharp, well-localized pain sensations quickly, while C fibers transmit dull, poorly localized pain sensations slowly.
• Pain receptors respond to noxious stimuli such as heat, cold, mechanical pressure, chemical irritants, or electrical currents.
• Chemicals like bradykinin, histamine, prostaglandins, serotonin, and substance P activate ionotropic receptors that open cation-permeable channels.
• C fiber activation leads to dull, poorly localized pain with delayed onset.
• Activated ion channels allow Na+ influx into the cell, leading to depolarization and generation of action potentials.
• Acute pain serves as an alarm system that warns us about potential tissue injury.
• There are two types of pain: acute (short-term) and chronic (long-lasting).
• Neurotransmitters released at synapses include substance P, glutamate, and calcitonin gene-related peptide (CGRP), among others.
• Endogenous opioids act on mu-opioid receptors located throughout the body, including the brain, spinal cord, and peripheral nerves.
• Sensitization occurs when repeated exposure to painful stimuli causes an increase in sensitivity to subsequent stimuli.
• Calcitonin gene-related peptide (CGRP) is involved in regulating blood pressure, body temperature, and immune function.
• Glutamate is the most abundant excitatory neurotransmitter in the central nervous system and plays a role in learning and memory.
• Substance P is involved in nociception and has been implicated in various neurological disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
• Substance P is a neuropeptide that acts as a neurotransmitter and has been implicated in various physiological processes such as inflammation, pain perception, and stress response.
• Pain is an unpleasant sensation signalling that the body is damaged or threatened with an injury.
• This noxious stimulation causes a release of chemical mediators from the damaged cells including: prostaglandin; bradykinin; serotonin; substance P; potassium; histamine.
• Primary sensory neurons release a peptide known as substance P that acts both as a neurotransmitter and as a modulator that enhances the pain pathway.
• The reticular system is responsible for the autonomic and motor response to pain and for warning the individual to do something, for example, automatically removing a hand when it touches a hot saucepan.
• The somatosensory cortex is involved with the perception and interpretation of sensations. It identifies the intensity, type and location of the pain sensation and relates the sensation to past experiences, memory and cognitive activities. It identifies the nature of the stimulus before it triggers a response, for example, where the pain is, how strong it is and what it feels like.
• Limbic system: This is responsible for the emotional and behavioural responses to pain for example, attention, mood, and motivation, and also with processing pain and past experiences of pain.
• Excitatory neurotransmitters released are adenosine triphosphate, glutamate, calcitonin gene-related peptide, bradykinin, nitric oxide, and substance P.
• Inhibitory neurotransmitters involved with the modulation of pain include endogenous opioids (enkephalins and endorphins), serotonin (5-HT), norepinephrine (noradrenaline), gamma-aminobutyric acid (GABA), neurotensin, acetylcholine, and oxytocin.
• Referred pains are activity in interneurons that leads to stimulation of the primary sensory cortex, so an individual feels pain in a specific part of the body surface.
• Pain can be referred from one area to another due to convergence of afferent fibres on second-order neurones in the spinal cord or brainstem.
• Acupuncture is a centuries-old Chinese therapy that is based on the manipulation of needles inserted in special locations on the body.
• Needles stimulate a type of sensory neuron and trigger the release of endorphins (morphine-like pain suppressants) by the brain.
• Acupuncture may also be useful for repairing neural damage following strokes and for treating drug and alcohol addictions.
• Aspirin inhibits prostaglandins and slows the transmission of pain signals from the site of injury
• Opiates act directly on opioid receptors in the brain, activating descending pathways that inhibit incoming pain signals.
• Endogenous pain modulation helps to explain the wide variations in the perception of pain in different people as individuals produce different amounts of inhibitory neurotransmitters.
• Endogenous opioids are found throughout the central nervous system (CNS) and prevent the release of some excitatory neurotransmitters, for example, substance P, therefore, inhibiting the transmission of pain impulses.