Pain Mechanisms & Clinical Correlations

Nociceptors

Free nerve endings (many are forms of chemoreceptors), responds to chemicals released by damaged tissue caused by overly intense stimuli

Fast Pain

Sharp, pricking, acute and electric pain. Stimuli: needle pricks, skin cut, burned or shocked. Not in deeper tissues

Slow Pain

Increases slowly and is slow burning, aching, throbbing, nauseous, and chronic pain. Tissue destruction.

Nociceptors

Pain receptors assosciated with free nerve endings (special form of chemoreceptors), respond to chemicals released by damaged tissue caused by overly intense stimuli (slowly adapting)

Receptor Fields

Each receptor has an area within which an adequate stimulus will activate the receptor (highest at the center). Nociceptor density varies in skin from different regions of the body. Inversely proportionate to the number of receptors (more receptors = smaller receptive field). High on fingertips while low on back.

A-delta fibers

Fast conducting pain system (myelinated) found primarily in skin

C - Fibers

Slow conducting pain system found deeper in the tissue (unmyelinated)

Pain Chemical Stimuli

Bradykinin, serotonin, histamine, K+, acids, ACh, proteolytic enzymes, prostaglandins and substance P

Bradykinin

Tissue damage releases enzymes that activate this. The activated form binds receptors on nociceptors that APs in the axon, causing pain. Stimulates prostaglandin release from nearby cells.

Histamine

Directly stimulates the nociceptor, causing pain. Causes local swelling by dilating blood vessels and opening pores in capillaries (fluid from blood leaks into tissue causing swelling)

Prostaglandins (Sensitive Pain Receptors)

K+ and bradykinin directly activate pain receptor ending, while this makes it more sensitive to these stimuli (+ feedback loop).

Block Synthesis of Prostaglandins

Aspiring and non-steroidal anti-inflammatory drugs

Pain Receptor Axon

Terminated on the dorsal horn of grey matter of spinal cord. Sends branches to skin that release substance P.

Substance P

Causes increase blood flow to the area. Sensory neuron releases glutamate and substance P onto neurons in the spinal cord that carry the signal to the brain. Brain perceives a subjective, unpleasant sensation that we interpret as pain.

Acute inflammation

Nonspecific response of tissue to injury (no matter the cause). NOT immune response

Rubor

Redness

Calor

Heat

Tumor

Swelling

Dolor

Pain

Signs of Inflammation

Rubor, calor, tumor, dolor, loss of function

Initiation

Substances are released from injured cells. Exposure of the basement membrane or CT components. Disruption of vascular integrity, microbial products, direct stimulus to mast cells and deposition of antigen/antibody complexes.

Transition Period of Vasoconstriction

Facilitates coagulation of blood, decreasing blood loss

Vasodilation

Increases local blood flow, causes redness and heat, increasing vascular permeability, leaky capillaries.

Edema

Accumulation of fluid in the extravascular spaces and interstitial tissue

Transduate

Fluid with little protein, clear serous fluid. With increased protein and cellular debris loss it becomes exudate

Exudate

Loss of plasma (fluid and proteins) from local capillary beds, as well as cells leads to viscous, and often pus

Major Components of Inflammation

Migration of WBC from vascular to injured tissue. Endothelium becomes “sticky” and leukocyte receptors bind to the sticky surface. Neutrophils accumulate beside the endothelial cell lining (margination). Leukocytes squeeze between endothelial cells into the interstitial space (emigration). Fosters phagocytosis of microorganisms and cellular debris.

Acute Inflammation Immediate Response

Deliver WBC to the injury site to clear infectious agents and necrotic tissue. Leukocytes may prolong the inflammatory response.

1st Order Pain Fibers

Nociceptors deliver pain to the spinal cord. Cell body in dorsal root ganglia, synapse at the level of entry.

Somatic

Sensory receptors within skin, bones, muscles, joints, eyes, and ears

Visceral Sensory

Convey impulses from visceral organs and blood vessels to the CNS for interpretation. Tongue and smell in the nasal epithelium are also visceral sensory.

Gate Theory of Pain

Relative balance between nociceptor and non-nociceptor signal. Promotes transcutaneous electrical nerve stimulation (TENS)

Transcutaneous Electrical Nerve Stimulation (TENS)

Electrical stimulation placed on skin activated large - diameter afferent fibers that overlap the area of pain

Substance P

NT that stimulates mast cells, mobile CT cells, often found near blood vessels, that release histamine

Capsaicin

Activates pain receptors on the tongue, causing them to release substance P at terminals in the medulla, producing a burning, painful sensation. Properties that block pain.

Pain Relieving Creams with Capsaicin

Zostric and Axsain

Fast Pain Second Order Neurons

Synapse with 1st order neurons in the dorsal horn and immediately decussate and ascend in the spinal cord. Terminate in the thalamus. NT is glutamate

Slow Pain Second Order Neurons

Terminate in the dorsal horn, synapse with other short fibers before decussating. Terminate in the brainstem. NT is glutamate and substance P

Brainstem

Slow pain second order neurons terminate. Includes reticular formation

Reticular Formation

An interconnected network of brainstem nuclei in the mesencephalon. Pain modulation and habituation

Pain Modulation

Pain route signals reach the cortex but descending pathways from the RF can block transmission signals.

Habituation

Ignoring inconsequential stimuli while remaining sensitive to others. Cardiovascular, somoatic motor control and cortical alertness.

Thalamus

Fast fibers terminate here. The order neuron carries the stimulus to the appropriate area of the cerebrum.

Dejerine-Roussy Syndrome

Thalamic syndrome causing spontaneous burning pain or abnormal sensations that are perceived as origination from body.

Parietal Lobe

The main function is to integrate different sensory inputs, assembling understanding (conscious awareness of pain). 3rd-order neurons carry input to the appropriate area of the post-central gyrus here. Receives somatic info from touch, pressure, pain, taste, and temperature receptors (spatial discrimination). Neurons from the post-central gyrus then carry input to the somatosensory association area (4th order neurons), posterior to the postcentral gyrus.

Parietal Lobe Damage

Difficulty in identifying objects by touch and lack of body awareness

Temporomandibular Joint Disorder

Associated with bruxism (grinding of teeth). Pain in the joint, the ear, face, or obit, with limited mandibular movement and TMJ sounds.

Post-Herpetic Neuralagia

Herpes zoster virus can lie dormant in neurons for years. The immune system is weakened as a result of age, stress, and the virus can travel back through the sensory axons to the skin, producing a rash. It could cause damage to sensory nerve fibers; light touch or temperature change can trigger pain.

Headaches

Cerebral vault, nasl sinus, tension, toxicity, migraine

Cerebral Vault

Meningitis, loss of cerebrospinal fluid

Nasal sinus or Eyes

Sinusitis, TMj can present as eye of facial pain, eye or orbit inflammation

Tension

Spasm of muscles of scalp and neck causing pain

Toxicity

Alcohol, drugs. CO

Migraine

Deep-seated and steady, slow pain. Reflex vasospasm of cranial arteries, blood pressure results in dilate and pulsation triggering pain.

Tic Douloureux (Trigeminal Neuralgia)

Stabbing pain over one side of the face in the area of CN V (CN IX), mainly in V1 and V2. Extreme pain sets off from sensitive trigger spots caused by compression of the nerve by an adjacent blood vessel, causing myelin degeneration.

Facial Nerve (CN VII)

Primary motor nerve to facial muscles and taste and sensory from anterior 2/3 of tongue. Autonomic motor function to lacrimal, nasal, and salivary glands

Bell’s Palsy

Loss of function by VII on one side. Pain behind ear and on one side of face may precede paralysis.

Analgesia Syndrome

The brainstem can send inhibitory signals down to the dorsal horns and block painful stimuli before they reach the brain. NT serotonin and enkephalins cause pre and post-synaptic inhibition at the dorsal horns.