Pain is a protective sensory experience that alerts the CNS to tissue injury or dysfunction. It can be classified as nociceptive (physiological response to stimuli) or neuropathic (due to nerve dysfunction).
Nociceptive Pain
-
- Definition: Pain caused by activation of nociceptors in response to mechanical, thermal, or chemical stimuli.
- Receptors: Transient receptor potential vanilloid (TRPV) receptors → cause Ca²⁺ influx → Na⁺ channel activation → action potential.
- Fibers involved:
- Aδ fibers → sharp, well-localized, acute pain.
- C fibers → dull, throbbing, chronic pain.
Phases of Pain Transmission & Pharmacologic Modulation
| Phase | Description | Example Drug Classes (Blockers) |
|---|---|---|
| Transduction | Conversion of painful stimulus into electrical activity in nociceptor endings | Local anesthetics, α2-agonists, gabapentinoids, NSAIDs, acetaminophen, and glucocorticoids |
| Transmission | Propagation of signal from the peripheral nerve → dorsal horn → brain | Local anesthetics, α2-agonists, opioids |
| Modulation | Amplification or suppression of pain signals in spinal cord pathways | TCAs, SSRIs, SNRIs, gabapentinoids |
| Perception | Conscious awareness of pain in the brain (thalamus, cortex) | α2-agonists, opioids, TCAs, SSRIs, SNRIs |
Neuropathic Pain
- Definition: Pain resulting from dysfunction or injury of the peripheral or central nervous system, independent of nociceptor activation.
- Mechanism: Upregulation and persistent activation of voltage-gated Na⁺ channels → ectopic neuronal firing.
- Example: Diabetic peripheral neuropathy.
Key Differences
| Feature | Nociceptive Pain | Neuropathic Pain |
|---|---|---|
| Cause | Tissue injury (mechanical, thermal, chemical stimuli) | Neuronal dysfunction/damage |
| Fibers | Aδ and C fibers | Aberrant neuronal firing |
| Mechanism | TRPV receptor → ion influx → Na⁺ channel depolarization | Voltage-gated Na⁺ channel upregulation |
| Examples | Burn, fracture, arthritis | Diabetic neuropathy, postherpetic neuralgia |
Learning Objective
By the end of this topic, you should be able to:
- Differentiate nociceptive vs neuropathic pain.
- Describe the fibers, receptors, and channels involved in pain transmission.
- Identify the four processes of pain transmission (transduction, transmission, modulation, perception) and the drug classes that act at each step.
- Recognize examples of nociceptive vs neuropathic pain conditions commonly tested on licensing exams.
