Dorsal horn secondary afferent.
Growth hormone-releasing hormone (GHRH).
Nociceptors are unmyelinated nerve endings that are abundant in skin and musculoskeletal tissue.
NMDA, AMPA, NK1, and adenosine (A1/A2) receptors.
Non-noxious (pressure/touch).
The 'gate' is opened presynaptically by C fibers via substance P and postsynaptically by Aδ fibers, which inhibit the action of enkephalinergic interneurons at the level of the substantia gelatinosa, allowing transmission of pain signals.
Unimodal nociceptors respond to pinprick and sudden heat.
Chemical stimuli can be exogenous (e.g., capsaicin) or endogenous.
They project to the somatosensory cortex and are responsible for conscious perception and memory of pain as well as its discrimination.
The spinomesencephalic tracts terminate in the midbrain and periaqueductal grey (PAG).
Binding directly to bacterial toxins and modulating receptors on host cells to prevent virus and bacteria penetration.
Circulating antigen–antibody complexes deposit in vessels and tissues, activating the classic complement pathway and inflammatory mediators.
Stimulates the release of follicle-stimulating hormone (FSH) and luteinising hormone (LH).
Glutamate, aspartate, and substance P.
Aδ fibers ascend and stimulate the PAG to exert its inhibitory action, explaining how acupuncture and low-frequency TENS may attenuate pain.
Stimulates the release of glucocorticoids (mainly cortisol) from the adrenal cortex.
They confer immunological memory, allowing for a faster and stronger response upon subsequent exposure to the same antigen.
Neuromuscular blockers, latex, antibiotics, dyes, and NSAIDs.
Neutrophils.
Reflexes are neuronal pathways that produce rapid, automatic, and predictable responses to a stimulus.
Axon diameter: 0.5–1 μm, Velocity: 0.5–2 m/s, Function: Pain and temperature.
Dorsal horn (presynaptic afferents) and Descending pathways: PAG (postsynaptic secondary afferents).
There is a defect in the ryanodine receptor, leading to uncontrolled release of Ca2+ from the sarcoplasmic reticulum, causing sustained muscle contraction and rigidity.
The bundles or fascicles within a skeletal muscle are surrounded by perimysium.
Inhibition of NMDA and Glutamate.
Thyrotropin-releasing hormone (TRH).
The 'gate' is closed by descending inhibitory fibers, peripheral Aβ fibers, and indirectly by the action of Aδ fibers on descending pathways, resulting in reduced transmission of pain signals.
Stimulates the thyroid gland to release thyroxine (T4) and triiodothyronine (T3).
Bradykinin, histamine, serotonin, acetylcholine, H+ and K+ ions.
Stimulation results in an influx of sodium and calcium ions, causing depolarization of the cell membrane and initiation of an action potential (AP).
The fibres terminate in the dorsal horn of the spinal cord and synapse with secondary afferent neurons in Rexed’s laminae.
Phagocytosis is the process of ingestion of a microorganism, another cell, or cell fragments by a phagocyte to form an intracellular phagosome, which fuses with a lysosome to digest the particle.
Monocytes.
The basic components of the reflex arc include a receptor, afferent sensory neurone, synapse, efferent motor neurone, and effector organ.
Somatic reflexes are reflexes that involve the skeletal muscle system, such as the knee jerk stretch reflex.
Stretch reflexes help maintain muscle tone, aid posture, and prevent injury by opposing overstretching of muscles.
The inverse stretch reflex refers to the relaxation of a muscle in response to a strong stretch. When muscle tension becomes too great, Golgi tendon organs inhibit the activity of efferent motor neurones to prevent muscle damage.
Reduced glutamate release from Aδ & C fibres and increased anti-nociceptive transmission via GABAergic inhibition.
Surface barriers, inflammatory response, and activation of the alternative complement pathway.
Aβ fibers inhibit C fiber input presynaptically via stimulation of GABA receptors. They are stimulated by touch/pressure and explain how 'rubbing it better' and high-frequency, low-amplitude TENS may attenuate pain.
Enkephalinergic interneurones inhibit postsynaptic transmission, leading to gate closure by activation of enkephalin-secreting interneurones.
The classical pathway is a specific immune response involving the binding of complement to antibodies on pathogens, while the alternative pathway is a non-specific response involving the binding of complement to carbohydrates on microbes, bacterial toxins, and certain drugs.
The AP is propagated along the nerve fibre via sodium and calcium channels to the dorsal root ganglion and the dorsal horn.
The influx of calcium causes the release of neurotransmitter into the synaptic cleft.
Circulating IgE and IgM bind to antigens, activating macrophages, NK cells, and the classic complement pathway, resulting in target cell lysis.
Acute and Chronic.
Pre-junctional nAChR located on nerve terminals form a positive feedback mechanism to increase ACh release during high activity, such as tetanic stimulation.
Neuropathic pain is due to dysfunction of the nervous system.
T cells become activated, begin to proliferate, and some branch into memory cells.
Tertiary afferents project to the somatosensory cortex.
It is a theory that postulates pain transmission from primary to secondary afferents is 'gated' by interneurons in the substantia gelatinosa, reducing the response to nociceptive stimuli.
Antibacterial enzymes in tears, saliva, and breastmilk; acidic environment of the stomach.
Enkephalins and gamma-aminobutyric acid (GABA).
The locus caeruleus (LC) is an important brainstem nucleus projecting descending inhibitory pathways to the dorsal horn via noradrenaline (α-adrenergic receptors).
Stimulates milk production.
It is an immediate or anaphylactic response where IgE antibodies on mast cells and basophils bind to an antigen, causing the release of histamines and other mediators.
The receptor undergoes a conformational change, opening the central ion channel to allow the passage of cations, predominantly Na+ and K+, causing localized depolarization of the muscle fiber membrane.
Persists beyond the time of healing or injury and has no clearly definable cause.
A motor unit refers to a single motor neuron and all the muscle fibers it innervates.
Serotonin and Endogenous cannabinoids – Prostaglandins.
The stretch reflex is a monosynaptic reflex that results in the contraction of a muscle in response to its being stretched. Muscle spindle receptors are stimulated, generating an action potential that propagates down afferent sensory neurones to the spinal cord, where they synapse with efferent motor neurones, causing the muscle to contract.
The resting membrane potential for skeletal muscle is –90 mV.
The resting membrane potential for nervous tissue is –70 mV.
Rexed’s laminae I (superficial) & V (deep).
Stimulates the liver to synthesize and release insulin-like growth factors (IGFs).
In females, it stimulates the production of oocytes and secretion of ovarian estrogen. In males, it stimulates sperm production.
Prostaglandins, leukotrienes, substance P, neurokinin A, and calcitonin gene-related peptide.
They produce and release millions of copies of antibodies into the circulation.
Blood transfusion reactions, erythroblastosis fetalis, autoimmune haemolytic anaemia, hyper-acute graft rejection, heparin-induced thrombocytopenia type 2, Graves’ disease, and myasthenia gravis.
Because not all nerve fibre types within the originally assigned group were the same.
Touch and pressure.
5HT3 and Cannabinoid – COX.
The Bell–Magendie law states that the anterior spinal nerve roots contain only motor fibres and the posterior nerve roots contain only sensory fibres.
Suppressor T cells are involved in the modulation of the immune response.
Axon diameter: 1–4 μm, Velocity: 6–24 m/s, Function: Pain and cold.
MOP opioid, 5HT1 & 5HT3, and α-Adrenergic.
Stabilisation of sodium channels.
Non-specific (or innate) and specific (or acquired/adaptive).
Skin, coughing and sneezing, tears, urine, and mucus.
Descending serotonergic (PAG, NRM) and noradrenergic (LC) fibers activate enkephalin-secreting interneurons, which inhibit postsynaptic transmission. This explains how antidepressants and opioids exert their effect.
The neurotransmitters involved include endorphins, enkephalins (acting on mu-opioid receptors), and serotonin (acting on 5HT1 and 5HT3 receptors).
Stimulates the darkening of the skin.
By binding to antigens expressed on pathogens, marking them for destruction by phagocytosis or the classic complement pathway.
Two heavy chains and two light chains, with a variable region at one end.
Neutrophils (50–70%), macrophages, monocytes (2–6%), eosinophils (1–6%), basophils (1%), mast cells, and natural killer (NK) lymphocytes.
A numerical system.
Specific immunity is antigen-specific, allowing for a stronger immune response that confers immunological memory for specific pathogens.
It is the process by which electrical activity of muscle depolarization results in mechanical changes leading to contraction.
Reciprocal innervation is the process where sensory neurones synapse with inhibitory inter-neurones that innervate the antagonistic muscle group, causing the antagonistic muscles to relax when the stretched muscle contracts.
A skeletal muscle is covered by a connective tissue called the epimysium.
Antibodies on the surface of B cells bind to specific antigens, forming an antigen-antibody complex that is taken up by the B cell and lysed, forming antigenic peptides presented on MHC 2 on the B cell surface.
Dorsal horn and Descending pathways.
C fibers.
It is the site of extensive modulation of pain and the 'gate control' theory of pain.
The 'gate control' theory of pain suggests that slow (affective) fibres synapse in the brainstem’s reticular formation and in intralaminar nuclei of the thalamus before projecting to the hypothalamus, limbic system, and autonomic centres. Tertiary fibres project to the cingulate gyrus in the cortex, associated with the affective-arousal component of pain.
In females, it stimulates ovulation, corpus luteum formation, secretion of ovarian estrogen, and secretion of corpus luteum progesterone. In males, it stimulates the secretion of testicular testosterone.
It is the process by which non-self-antigens are recognized, leading to an antigen-specific immune response.
Pressure, vibration, and proprioception are carried by Aβ fibres from the periphery, ascending in the dorsal columns ipsilaterally.
Contact dermatitis, chronic transplant rejection, and the immune response to TB.
Extra-junctional nAChR rapidly sprout after denervation and burns injuries.
Because these receptors are extremely sensitive to depolarizing neuromuscular blocking agents, which can result in profound hyperkalaemia.
Nociceptive pain is due to noxious stimulation of nociceptors. It is subdivided into superficial somatic pain, deep somatic pain, and visceral pain.
NK cells destroy tumor cells and cells infected by viruses.
Helper T cells and killer T cells.
Ca2+ binds to troponin, causing a conformational change in the troponin–tropomyosin complex, exposing myosin binding sites on actin filaments, allowing myosin heads to bind to actin and perform the power stroke.
Rigor mortis occurs due to the lack of ATP, which prevents the detachment of myosin heads from actin, holding the filaments in sustained contraction.
MOP opioid and GABA receptor.
0.5–2 ms⁻¹.
Nociceptors are classified as unimodal (thermo-mechanoreceptors) and polymodal.
Eicosanoids and cytokines.
In the ventral posterior nucleus of the thalamus.
Slow fibres may ascend in the spinoreticular tract, terminating in the reticular formation and thalamus.
An abnormal immune response, including allergies and autoimmunity, that damages the body’s own tissues.
Alphabetically into A, B, or C fibre types.
Superficial somatic pain is well-localised, sharp pain originating from the skin.
Deep somatic pain is dull, aching, and poorly localised pain originating from ligaments, tendons, and muscles.
Sensory from muscle spindle (annulospiral).
Inhibition of COX and Prostaglandins.
Tissue damage releases mediators that initiate and sensitise receptor stimulation, leading to the generation of an action potential.
Killer T cells bind to antigen-MHC class 1, and helper T cells bind to antigen-MHC class 2.
Activated killer T cells release cytotoxins, resulting in apoptosis of the host cell.
Helper T cells release lymphokines, which activate the B cell.
Non-specific immunity responds to pathogens in a generic way and does not confer long-lasting immunity, while specific immunity is antigen-specific and confers immunological memory.
Stimulates the release of prolactin.
Polymodal nociceptors respond to pressure, heat, cold, chemicals, and tissue damage.
It results in opsonisation of target cells, disruption of their cell membrane phospholipids, attraction of immune cells, and increased vascular permeability.
In lymph nodes, spleen, and bone marrow.
The kidney contains two portal circulations: an afferent arteriole enters the Bowman's capsule and forms the glomerulus (primary capillary bed). The efferent venule leaving the glomerulus enters two secondary capillary beds: one surrounding the cortical tubular system and another surrounding the loop of Henle (vasa recta). These circulations maximize the reabsorption of water and electrolytes filtered at the glomerulus.
IgG, IgM, IgE, IgA, and IgD.
Pain is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage’.
Nociceptive and Neuropathic.
Central and Peripheral.
Axon diameter: 2–5 μm, Velocity: 10–30 m/s, Function: Pain and temperature.
Sensory from Golgi tendon.
Sensory from muscle spindle (flower-spray).
Pain and temperature.
Inhibition of reuptake of serotonin and noradrenaline.
The enzyme acetylcholinesterase is found in the synaptic cleft.
Presynaptic inhibition in dorsal horn by Aβ fibres, involving GABA.
Small, 2–5 μm.
Adenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH).
Lower gastrointestinal tract bacterial flora that prevents overgrowth of pathogenic bacteria.
Redness, swelling, heat, and pain.
Other B cells, plasma cells, and memory cells.
ADH helps to retain water in the body by reducing urine production and increasing water reabsorption in the kidneys.
The main descending pathway is the periaqueductal grey (PAG) in the midbrain, which receives projections from the thalamus, hypothalamus, amygdala, and cortex, and delivers projections to the nucleus raphe magnus (NRM) in the medulla.
Serum sickness, systemic lupus erythematosus, rheumatoid arthritis, and glomerulonephritides.
Macrophages act as scavengers of worn-out cells, destroy foreign material by phagocytosis and extracellular release of toxic chemicals, release cytokines and complement protein, and activate the adaptive immune system by acting as antigen-presenting cells (APCs).
The normal ε subunit is replaced by the fetal γ subunit.
Motor to muscle spindles.
Autonomic (pre-ganglionic).
T and B lymphocytes, plasma cells, antibodies, the classic complement pathway, and immunological memory.
The action potential traveling down the T-tubules triggers calcium release channels (ryanodine receptors) on the sarcoplasmic reticulum to open.
Nociceptors are receptors that respond to noxious stimuli, which may be thermal, mechanical, or chemical.
Synaptic transmission with secondary interneurones occurs in Rexed’s laminae.
Muscle fibers have a striated appearance due to the presence of numerous myofibrils.
Nicotinic acetylcholine receptors (nAChR) are located at the crests of the folds in the motor end plate of the muscle fibre.
Spinothalamic tracts (STT).
Substance P is involved in presynaptic gate opening.
The more heavily myelinated the nerve fibre is, the faster the impulse transmits.
The cell bodies lie in the dorsal root ganglia.
It is a cell-mediated immune response involving T cells that become activated on re-exposure to an antigen, causing tissue damage.
Recent onset, limited duration, and identifiable cause related to injury or disease.
Both release histamines in response to allergens.
Visceral pain is cramping pain with varying localisation, often associated with referred pain and autonomic stimulation, originating from organs and viscera.
T cells recognize pathogens only after antigens bind to specific receptors (MHC) on the surface of antigen-presenting cells (APCs).
An action potential is propagated along the primary afferent nerve fibres (C & Aδ) to the dorsal horn of the spinal cord.
Secondary interneurones decussate and travel in the anterolateral spinothalamic tracts through the brainstem to the thalamus.
Peripheral nerves.
When a motor nerve is depolarized, voltage-gated Ca2+ channels open in the presynaptic membrane, allowing Ca2+ to enter the nerve terminal and enable vesicles to fuse and release their contents by exocytosis.
The action of ACh is rapidly terminated by acetylcholinesterase within the synaptic cleft.
Axon diameter: 10–20 μm, Velocity: 60–120 m/s.
By extracellular release of enzymatic granules.
Visceral reflexes are reflexes that involve the autonomic nervous system, such as the pupillary light reflex.
Nociceptor.
The resting membrane potential for cardiac muscle is –90 mV.
Dorsal horn and Descending pathways.
Descending fibres from the cortex, thalamus, and brainstem exert an inhibitory influence on pain transmission in the dorsal horn.
LC (Locus Coeruleus).
The withdrawal reflex is a polysynaptic reflex that responds to a painful stimulus. Nociceptors are stimulated, and impulses travel along sensory fibres to the spinal cord, where they synapse with inter-neurones that activate motor neurones, causing the flexor muscles of the affected limb to contract. The cross-extensor reflex also activates the contralateral limb to maintain balance.
Muscle fibers in skeletal muscle are 10–100 μm in diameter.
An immediate polysynaptic withdrawal reflex occurs at the level of the spinal cord as some interneurones connect to motor neurones at many levels. This is a protective reflex.
ACh is synthesized within the axoplasm from choline and acetyl coenzyme A in a reaction catalyzed by choline-O-acetyltransferase.
Activated helper T cells release cytokines that activate killer T cells, B lymphocytes, and macrophages.
The basic contractile unit of a skeletal muscle is the sarcomere.
α2-Adrenergic agonist and Noradrenaline.
Some spinal ascending fibres transmit impulses to the reticular-activating system and to higher centres involved with affect, emotion, and memory.
Binding (blocking) to voltage-gated calcium channels and promoting noradrenaline-mediated inhibition.
Myofibrils are formed by thick (myosin) and thin (actin) contractile filaments in association with the regulatory proteins tropomyosin and troponin.
Peripheral nerve fibre.
Approximately 80% of ACh is stored in vesicles available for release, with some vesicles at 'active zones' for immediate release and others in the 'reserve pool'.
The neuromuscular junction is composed of the α-motor neurone, synaptic cleft, and motor end plate of the muscle fibre.
Blocking sodium channels.
