Theories of Pain

• Pain is a complex phenomenon with no single theory fully explaining the experience.

Theories of Pain

• Specificity theory, pattern theory, gate control theory, and neuromatrix theory are all proposed theories.
• Pain defintion by Sternbach and the International Association on Pain (1968): An abstract concept including personal sensation of hurt, stimuli signaling tissue damage, and protective responses.
• Ronald Melzack's view: Pain is not a fixed response but is modified by experiences, expectations, and culture.
• McCaffery's definition: Pain is whatever the experiencing person says it is, whenever they say it exists.
• IASP's 2020 definition of pain: An unpleasant sensory and emotional experience associated with actual or potential tissue damage.
• Biological, psychological, and social factors play a role in a personal experiences of pain.
• Pain cannot be inferred based on sensory neuron activity alone, as pain and nociception are different.
• Individuals learn the concept of pain through life experiences.
• A person's self-report of pain should be respected.
• Pain usually serves an adaptive role, but this is rare.

Classification of Pain: Location

• Cutaneous: Affects skin and subcutaneous tissues, sharp, bright, well-localized due to nociceptors.
• Deep somatic: Affects periosteum, muscles, tendons, ligaments, and joints, is diffuse, throbbing, and may radiate.
  • Periosteum and joint capsules are most sensitive.
  • Tendons, ligaments and subchondral bone are less sensitive.
  • Muscle and cortical bone are less sensitive
  • Synovium, articular cartilage and fibrocartilage are almost insensitive.
• Visceral: Originates from internal organs, is diffuse, poorly defined, stems from stretching, distension, or ischemia, and can exhibit referred pain.

Classification of Pain: Duration

• Acute: Sudden onset from trauma, surgery, or inflammation. Serves as a warning of possible tissue damage, short-lived, well-localized. Initiates an autonomic response. Sharp, stabbing nature turning achy and subsides as the injured area recovers.
• Chronic: Onset may be sudden, but usually develops insidiously; lasting longer than should, transmitted by small unmyelinated C-fibers. Unknown cause is related to sensory processing signals within the nervous system. Is poorly localized, causing dull aching, nagging, tiring pain.

Classification of Pain: Other

• Localized: Confined to the site of origin.
• Projected: Travels along a specific nerve.
• Radiating: Diffuse around the site of origin, not well delineated.
• Referred: Perceived in an area distant from the site of painful stimuli where many impulses converge leading to the origin being indistinguishable by the brain.
• Phantom Limb: Follows amputation of limb/part of limb.

Pain Pathways

• Nociception = Pain sense, activation of nociceptors.
• Nociceptors = Pain receptors, non-encapsulated free nerve endings.
• Nociceptors respond to mechanical, thermal, and chemical stimuli, and are unevenly distributed throughout the body. Skin is more sensitive than internal structures due to more nociceptors.
• Nociceptors do not adapt to stimulation, unlike other receptors.

Neuropathic Pain vs. Nociceptive Pain

• Nociceptive pain develops when nociceptors are stimulated by damaged cells/tissues.
• Neuropathic pain occurs when there is damage or dysfunction in the peripheral or central nervous system (e.g. nerve compression), and is considered a chronic pain condition.

Nerve Fibers

• A-fibers: Large myelinated fibers found mainly in spinal nerves, include motor, proprioceptive, touch and pressure sensations.
  • A (α) Alpha fibers transmit motor impulses and proprioceptive information.
  • A (β) Beta fibers transmit touch and pressure sensation.
  • A (γ) Gamma fibers transmit touch and motor excitation of muscle spindles.
  • A (δ) Delta fibers transmit pain, heat, cold and pressure sensations.
    • A-delta fibers: conduct pain impulses at 10 – 30 meters/sec, called fast pain fibers, producing sharp, stabbing, and localized pain sensations.
• B-fibers: Smaller myelinated fibers found mainly in the pre-ganglionic fibers of the ANS, transmit motor impulses only, and are not involved in pain pathways.
• C-fibers: Small unmyelinated fibers that transmit pain and itch sensations at .5 - 2.5 meters/sec called slow pain fibers. Comprise more than half the sensory fibers in peripheral nerves and all post-ganglionic fibers of the autonomic nervous system, producing diffuse, dull, and aching pain.
• Pain transmission occurs along both A-delta fibers and C-fibers.

Transmission Of Pain:

• Acute pain information travels through the central nervous system from the nociceptor, involved with two functions (see slides on chronic pain for comparison.)
• Reflex motor response: First-order neurons synapse with motor neurons (with or without an intervening interneuron) to cause a rapid muscle contraction to remove an injured body part away from possible harmful substances.
• Alerting the brain that tissue damage is occurring or about to occur: the message goes to the brain leading to pain perception through the sensory/discriminatory, motivational/affective, and cognitive/evaluative systems along with pain modulation.

Pain Pathways In The Brain

• First, primary-order neurons (SN #1) enters the spinal cord via the dorsal root of a spinal nerve.
• Next, once in the dorsal horn of the spinal cord, SN#1 releases neurotransmitters: Substance P and Glutamate.
• Then, second-order neurons (SN #2, interneurons) carry the pain impulses to the opposite side of the spinal cord.
• SN#2 carries pain impulses up the spinal cord in the anterior and lateral spinothalamic tracts (*also carries temperature and crude touch sensations).
• In the spinal cord and brain, the spinothalamic tract consists of two separate pathways:
  • Neospinothalamic: tract for FAST PAIN.
  • Paleospinothalamic: tract for SLOW PAIN.
• Fast pain fibers form the neospinothalamic tract and terminate in the thalamus, with the third-order neuron carrying pain impulses to the primary somatosensory area of the cerebral cortex to provide information regarding the determination of pain.
• Slow pain fibers take a different route, forming the paleospinothalamic tract, passing through the reticular formation in the brain stem before terminating in the thalamus. The third-order neuron completes the journey and perception of diffuse, dull achy pain is felt in the cortex.
  • Synapses occur with many different areas of the cerebral cortex.
  • Synapses also occur with neurons in the limbic system as well as the hypothalamus.

Modulation of Pain

• Pain modulation: The process of suppressing or facilitating pain within the brain and spinal cord.
• Pain suppression can be brought about naturally by strong emotions, stress and other factors.

Pain management

• Pain management concentrates on the patient's response to pain, aiming to reduce anxiety to avert depression or anger.
  • Altering the pain message at the periphery: Use heat to increase blood flow or cold to reduce swelling and numbness
    • NSAIDs usage inhibits arachidonic acid cascade to prostaglandins.
    • Applying local anesthetics at nerve endings or nerve plexus
  • Altering the message at the spinal cord: Epidural, massage, TENS
  • Altering the message in the brain: Systemic opioids, anti-depressants, and/or cannabinoids.
  • Implementing stress reduction, relaxation therapy, distractors, massage, physiotherapy, exercise, hypnosis imaging, acupuncture, TENS
  • Administering sedatives and anti-anxiety drugs.

Endogenous Analgesia

• Endorphins – Beta-endorphin, enkephalins and dynorphins inhibit pain impulses centrally and peripherally: these are endogenous morphine-like molecules (opioids) that bind to the same opiate receptors as morphine and other pain-relieving chemicals. Enkephalins and dynorphins can be found in Periaqueductal gray matter ( PAG, endogenous analgesic center) in the midbrain, spinal cord and medulla
  • Beta- Endorphin is a large polypeptide synthesized in the hypothalamus, the limbic system, and the pituitary gland. This substance binds with opiate receptors and leads to a reduction of the transmission of pain; also released during sustained exercise to give a sensation of euphoria
  • Enkephalins are smaller molecules, some of which inhibit the release of substance P in the spinal cord.
  • Dynorphins are opioids released in many parts of the brain including the hippocampus and the amygdala and are strongly related to CRH, therefore, playing a role in fear and stress.
  • Acupuncture and TENS (transcutaneous electrical nerve stimulation) are effective in managing pain because they elicit the release of endogenous opiates. The release of endogenous opiates is thought to be involved in some aspects of the placebo effect.
  • Chemicals known as endocannabinoids involved in pain modulation as they bind to CB1 receptors in Central Nervous System controlling processes including a reduction in pain transmission.

Gate Control Theory

• Proposed by Melzack and Wall. The theory postulates that there is a “gate” to modulate input at the level of the spinal cord and possibly other areas of the CNS.
• When interneurons in the spinal cord are activated by large type A beta fibers carrying touch impulses, pain impulse transmission by small C fibers is blocked (i.e. gate is closed), this explains part of the efficacy of massage in relieving pain.
• TENS also stimulates the A beta fibers to help relieve pain.

Sensitization

• Sensitization: Mechanisms that facilitate pain signals to be created or to increase the intensity of pain perception.
  • Can occur at nociceptors (peripheral sensitization) or in the central nervous system (central sensitization)
• Thought to be involved in the production of chronic pain syndromes.

Etiology Of Pain Stimulation

• Ischemia within organs leads to hypoxia and lactic acid build-up, with nociceptors stimulated by H+ (heart)
• Distension or contraction of hollow organs (mechanical pressure/reducing blood flow to the smooth muscle)
• Temperatures above over 43°c
• Nerve compression/entrapment causing neuropathic and radicular pain.
• Inflammation from muscle strains or ligament sprains cause the release of chemicals that either stimulate or sensitize nociceptors.

Natural Agents That Activate or Sensitize Nociceptors

• Potassium, serotonin, bradykinin, histamine, prostaglandins, leukotrienes, and Substance P are naturally occurring agents that activate or sensitize nociceptors.

Pain And Medications

• Corticosteroids: Lipid-soluble medications that block arachidonic acid, thus decreasing inflammation.
• Aspirin and NSAIDs block the production of prostaglandins and thromboxane to reduce pain, inflammation, and fever.
• COX medications like NSAIDs decrease prostaglandins thereby decreasing pain, inflammation & fever. -COX inhibitors bind reversibly to enzymes -COX-1 is found in all tissues -COX-2 is induced by inflammation