Nociception vs. Pain: Key Differences

Nociception vs. Pain: Key Concepts

• Nociception and pain are often used interchangeably, but they are distinct concepts.
• Understanding the difference is crucial for clinicians and anyone interested in pain management.

Historical Perspective

• Pain was initially viewed as a simple sensory experience.
• Recent research has highlighted the complexity of pain, recognizing it as more than just a signal.

Definitions

• Pain (International Association for the Study of Pain definition): An unpleasant sensory and emotional experience associated with actual or potential tissue damage.
  • Pain has an effective component, incorporating emotions and other factors.
  • Tissue damage doesn't necessarily need to be present for pain to be experienced.
  • Pain serves as a warning system to protect against potential harm.
• Nociception: Physiological process of detecting noxious (harmful) stimuli that may damage tissue.
  • Noxious stimuli can be chemical, mechanical, or thermal.
  • Nociception is objective and measurable, while pain is subjective.
• Pain relies on interpreting objective nociception and is shaped by experience, emotions, and individual factors.

Nociceptive Pathway to the Brain

Nociceptive Receptors

• Nociceptors detect noxious stimuli.
• These pick-ups can be chemical, thermal, or mechanical.
• Free nerve endings within tissues have the ability to detect these stimuli.
• Different thresholds exist to distinguish between normal sensations and pain.

Nociceptive Fibers

• Two major types of nociceptive fibers: A Delta and C fibers.
• These fibers transmit nociceptive signals to the brain.
• Alpha fibers are thick and highly myelinated for fast signal transmission (e.g., proprioception).
• A Delta fibers are myelinated, smaller axons, and transmit signals at 6-30 meters/second.
  • A Delta fibers are responsible for rapid notification of damaging stimuli.
• C fibers are unmyelinated (but clustered within myelin) and transmit signals slowly (0.5-2 meters/second).
  • C fibers are responsible for ongoing, throbbing pain associated with tissue damage.

Speed and Function

• Proprioceptive fibers need to be fast for coordinated movement and reflexes
• Nociceptive fibers, while slower, provide a warning system and influence behavior.
• A Delta fibers prevent further immediate damage with rapid, specific responses.
• C fibers provide ongoing awareness of potential injury, promoting caution.

Nociceptive Pathway Anatomy

• Pricking a finger stimulates mechano nociceptors, sending a signal via A Delta fibers.
• Three-neuron chain carries the nociceptive signal to the brain:
  • First-order neuron: From fingertip to the spinal cord.
  • Second-order neuron: Synapses in the spinal cord, crosses to the contralateral side, ascends via the spinothalamic tract to the Thalamus.
  • Third-order neuron: Relays the signal from the thalamus to the somatosensory cortex.
• The thalamus acts as a sorting center, directing the signal to the appropriate area of the cerebral cortex.
• Tactile stimuli help localize source of pain
• Important neurotransmitters in this process: glutamate and substance P.
• Glutamate binds to the second-order neuron, causing an influx of sodium and calcium, initiating an action potential.

Consequences of Tissue Damage

• Tissue damage (e.g., pricking a finger) leads to inflammation.
• Damaged cells release chemicals, including histamine, prostaglandins, bradykinin, potassium, and ATP.
  • If ATP or potassium are injected in the area pain will result.
• These chemicals stimulate nociceptors and lower their threshold, making them easier to activate.
• C fibers are more dominant with chemical stimuli, resulting in throbbing pain. Inflammation and sensitization continue to worsen the pain response.

The Painful Experience in the Brain

• Both A Delta and C fibers send signals to various brain areas, shaping the experience of pain:
  • Reticular Formation: Affects sleep-wake cycles, making it difficult to sleep when in pain.
  • Hypothalamus: Triggers autonomic nervous system responses (fight or flight), affecting heart rate, blood pressure, etc.
  • Amygdala: Processes the emotional response to pain (pleasant vs. unpleasant).
  • Insular Cortex: Involved in the emotional experience of pain.
  • Anterior Cingulate Cortex: Cognition and emotional processing of pain.
  • Prefrontal Cortex: Influences cognition and behavior related to pain.
• Pain is a subjective experience, and has an affective nature. Also, pain is influenced by prior experiences and potential future events.
• Painful experiences do not have a one-to-one relationship.

Bush Walk Example

• Pain experience is heavily influenced by expectations and emotional state, not solely by the nociceptive signal.

Areas of the Brain Involved in Pain

• Thalamus, somatosensory cortex, amygdala, insula, anterior cingulate gyrus.
• Pain management must consider the psychology of the patient.

C Fiber Pathways

• A quarter to a tenth of C fiber neurons make it all the way up to the thalamus/cortex.
• The remaining C fibers trigger effects suggestive of suffering and pain without involving high brain centers.
• Cordotomies: Cutting the spinothalamic tract may provide temporary relief, but pain often returns.
• Silent neurons may also carry pain information, contributing to the return of pain after cordotomies.

Sensory Adaptation

• Nociception is unlike other sensory inputs (smell, touch, sight, taste).
• Other senses lead to desensitization with continued exposure.
• Nociception leads to sensitization, where the pain gets worse.

Sensitization

• The more a tissue is stimulated, the easier to stimulate it becomes.
• Chemicals released upon tissue stimulation (prostaglandins, histamines, bradykinins, etc.) lower nociceptor thresholds.
• Peripheral Sensitization: Altered nociceptor thresholds in the periphery.
• Spinal Cord/Brain Sensitization: Little circuits are created that continue to release chemicals and stimulate even if tissue damage is resolved.
• "No pain, no gain" is not a good mentality because chronic pain can occur after ignoring pain signals.

Treating Pain

• The approach should not just address the physiology, but must also address the affective nature, emotions, cognition, and behavior

Nociception: Four Steps

• Transduction: Stimuli becomes the action potential.
• Transmission: Sends the action potential up into the CNS.
• Perception: How that harmful experience translates into physical/behavioral changes.
• Modulation: Internal changes from the body to lessen nociception.

Descending Inhibition (Endogenous Opioid System)

• An endogenous process aims to dampen pain.
• Ascending nociceptive signals stimulate the periaqueductal gray matter (PAG).
• PAG sends a descending signal of neurons to the Rafi nuclei.
• Rafi nuclei is filled with serotonin producing neurons and travel to spinal chord.
• Serotonin speaks to the third neuron which stimulates the release of endogenous opoids (Endorphins, encephalins, dinorphins).
• Those opoids bind to the opoid recptors (Mu, Delta & Gamma) and the bind inhibits pain signals from travelling.
• That stops the pre-synaptic neuro transmission from coming across, thus inhibiting pain
• Opiates mimic opioid-like chemicals in our bodies exogenously by binding to opioid receptors
• Euphoria and dysphoria side effects can occur from those opiates can distract receptors in transmitting pain.
• Opioids will blunt not only the feeling of pain but also effect the individuals control of breathing.
• Norepinephrine works in conjunction with Serotonin in the descension of the pain signal.

Pain Classification

Acute vs Chronic Pain:

• Classified by the duration and degree of sensitization of the pain.
• Acute Pain: Pain after tissue injury that resolves once damage is healed.
• Chronic Pain: If pain remains for more than 3 months of tissue damage after there has been healing

Agent Leading to Pain:

• Inflammatory Based Pain: Pain caused by tissue inflammation.
• Neuropathic Pain: A nerve lesion/trauma/compression causes pain.
  • Diabetic neuropathy and Shingles are forms of such pain.
• Noci Plastic Pain: Is a form of chronic pain but where the original cause is unknown.
• Referred and Phantom Pain, both are types of pain.

Referred Pain

• A painful experience felt elsewhere on the body where no specific injury has occurred.
• Pain is caused by somatic or visceral factors.
  • An example is a heart attack, where the pain is felt in other regions.
  • Blood flow is stopped during attack, the ischemic cells produce metabolic byproducts which stimulates the nerves in your heart muscles.
  • There is poor mapping of the viscera and heart in the brain.
  • The nerve innervating the heart branches from the nerve from your connective tissue, which creates pain because the nerves intertwine.

Assessing a Patient for Pain via "PQRST"

• P stands for Provoking pain (what brought pain on).
• Q stands for quality of pain (how bad is it?)
• R stands for radiating (does the pain move along the body?)
• S stands for severity (scale of 0 to 10 on if pain is apparent)
• T stands for amount Of time.
• U stands for understanding (what is your knowledge on the pain and its potential origin)

Phantom Pain

• When a person has pain that is not associated with their body and specifically at a amputated limb.
• Somatosensory map on the brain exists, but the limb does not.
• With no sensory input from the amputated area, the brain amplifies any small signals.
• The damaged tissues release amplifying signals, making the area more sentive.

Ways to Stop Pain/Mitigate

• There are drugs that can inhibit the pain signals.
• Example is prostaglandins causing fever and can cause the cells to trigger nociceptors.
• Prostanglandins cause blood vessels to dilate so blood can pass through for regeneration or clean up of tissue.
• To mitigate pain one can get rid of prostaglandins or inhibit them by inhibiting the Cox 1 and Cox 2.
• Cox 1 creates prostatglandins creates membrane for for your gut and keeps your kidneys being perfused.
• Cox 2 causes inflammation or a fever or a pain response.
• Aspirin is a common drug that targets these prostaglandins, but is known to not have a select effect on prostaglandin but has an anti-clotting affect.
• Non steroidal anti inflammatory drugs create specific cox-inhibitors.

Mirror Box Therapy

• The visual cortex can override all sensory output
• Putting someones arm in a mirror box enables the non-existant arm to exist.
• Visual cortex can enable the pain the limbs were experincing.
• Visual experience can override sensory aspects, such as twitching or stretch of limbs, which helps mitigate pain.

Spinal Cord Injury

• Spinothalamic tract crosses to the other side of the medulla to the cerebral cortex.
• Touch signal travels up until the spinal chord until signal happens.
• Clinical relations help better determine what spinal injury a individual may have.
• Brown-Séquard Syndrome is when pain/temperature and touch pathways have no sensations