PATH1016 - PAIN 2025-26 Lecture Notes

Pain is defined as whatever and whenever the person says it is.
It is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

The Somatosensory system provides the Central Nervous System (CNS) with information regarding the body, specifically relating to:
- Touch
- Temperature
- Pain
- Body position
Sensory information is transmitted via three levels of neurons:
- First-order neurons: Carry signals from the periphery to the spinal cord.
- Second-order neurons: Carry signals from the spinal cord to the thalamus.
- Third-order neurons: Carry signals from the thalamus to the cerebral cortex.
The Dorsal root ganglion is the site of the first-order neuron body.
The somatosensory cortex is the final destination for third-order neurons where tactile and pain information is processed.

Specificity theory:
- Special pain receptors called nociceptors detect pain.
- The intensity of the pain is directly related to the amount of tissue injury.
- This theory is primarily used to describe acute pain.
Pattern theory:
- Sensory receptors create pain signals when stimuli are too strong.
Gate control theory:
- Pain is carried by distinct fibers in the spinal cord.
- A "spinal gate" regulates the transmission of pain to higher centers in the CNS.
Neuromatrix theory:
- The brain identifies pain.

Nociceptors (free nerve endings) respond to three main types of noxious stimuli:
- Mechanical: Intense pressure applied to the skin or extreme stretching of muscles.
- Thermal: Extreme heat or cold.
- Chemical:
  - Associated with tissue trauma, ischemia, and inflammation.
  - Involves specifically released mediators such as $K^+$ ions, $H^+$ ions, prostaglandins, leukotrienes, histamine, and bradykinin.
Chemical mediators are released by injured or inflamed tissue and act by stimulating nociceptors.
Aspirin and NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) are effective in controlling pain because they block the specific enzyme needed for prostaglandin synthesis.

Stimulation of nociceptors occurs due to noxious stimuli.
Noxious stimulation causes damaged cells to release chemical mediators:
- Prostaglandins
- Serotonin
- Substance P
- Histamine (released from mast cells)
An action potential is initiated, and impulses begin to move along the nerves.
Impulses are mediated by neurotransmitters, specifically glutamate and $Substance\,P$ .
Summary: Tissue injury $\rightarrow$ inflammation $\rightarrow$ mediator release $\rightarrow$ nociceptor stimulation.

Impulses travel from the spinal cord towards the brain via nerve fibers:
- A-delta fibers: Large, myelinated fibers. They transmit "fast pain" or "first pain" quickly. They release glutamate at the synapse with spinal neurons and use the neospinothalamic tract.
- C fibers: Small, non-myelinated fibers. They transmit "slow pain" more slowly. They release both glutamate and $Substance\,P$ and use the paleospinothalamic tract.
Anterolateral Pathways:
- Neospinothalamic tract: Fast conduction; travels to the thalamus and parietal cortex. It allows for the localization and identification of pain.
- Paleospinothalamic tract: Slower conduction; travels to the reticular activating system (RAS) and limbic system. It affects arousal, mood, and attention.

Pain signals enter the brain, and the sensation reaches consciousness.
The thalamus is responsible for the sensations of hurtfulness.
The parietal cortex and limbic cortex manage the meaningfulness of the pain and the emotional experience of pain.

This is the process of dampening or amplifying pain-related nerve signals.
Pathways start in the midbrain and brain stem and descend to the spinal cord.
Modulation takes place primarily in the dorsal horn of the spinal cord with inputs from ascending and descending pathways.
CNS Mechanisms:
- Periaqueductal gray (PAG) region: Located in the midbrain, it contains a high number of opioid receptors. It produces analgesia through the release of endogenous opioids.
- Rostral medulla: Axons descend to the dorsal horn to inhibit pain impulse transmission. Serotonin acts as an inhibitory neurotransmitter here.
- Endogenous analgesic mechanisms: Opioid receptors and opioid peptides (endorphins, enkephalins) are found in afferent neurons and the CNS.

Cutaneous pain: Superficial pain originating from the skin.
Deep somatic pain: Originates from deeper structures such as muscles or bones.
Visceral pain: Originates from internal organs.
Referred pain: Pain perceived at a site different from its point of origin (based on dermatomes).
Dermatomes: Areas of the body wall where sensation is supplied by a single pair of dorsal root ganglia.
Neuropathic pain: A complex, chronic state often accompanied by tissue injury where nerve fibers themselves are damaged, dysfunctional, or injured (e.g., nerve entrapment, compression, or neuralgias).
- Causes: Pressure on nerves, physical or chemical injury to neurons, infection, ischemia, inflammation, or neurotoxic drug treatments (e.g., cisplatin, paclitaxel, vincristine).
- Associated conditions: Diabetes, long-term alcohol use, hypothyroidism, renal insufficiency.
Neurogenic Inflammation: Tissue damage leads to inflammatory mediators stimulating nociceptors; impulses run up C fibers, and a dorsal nerve root reflex causes mediators to move back down and be released into tissues.

Definition: Severe, brief, and often repeated throbbing/shocking pain follows the path of a spinal or cranial nerve due to irritation or damage.
Trigeminal neuralgia: Causes stabbing or electric-shock-like pain in parts of the face due to trigeminal nerve damage or irritation. Treated with carbamazepine.
Post-herpetic neuralgia: Caused by a herpetic infection (shingles). Treated with antivirals or tricyclic antidepressants.

Acute Pain: Should be managed aggressively, collaboratively, and proactively. Includes assessment and reassessment using drug and non-drug therapies.
Chronic Pain: Requires early attempts to prevent pain. Management is often a team approach including:
- Neural blockade
- Electrical modalities
- Physical therapy
- Cognitive behavioral interventions
- Non-narcotic and narcotic medications
General Principles:
- Routine assessment is mandatory.
- Unrelieved pain complicates recovery.
- Self-report is the most reliable indicator of pain.
- Health Care Professionals (HCP) must assess, accept, and document pain.
- Treatment should be based on the patient’s goals.

Children: They feel pain starting in the neonatal period. Pain management must be dosed according to weight.
Older Adults: Prevalence of pain increases with age. Common causes include MSK disorders (arthritis, chronic low back pain) and neurologic conditions (diabetic neuropathy, postherpetic neuralgia). Polypharmacy must be considered when prescribing analgesics.