9. Pain Pathways: Periphery and Sensitization

Pain (IASP Definition)

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage, emphasizing its subjective and multidimensional nature.

Nociceptive Pain

Pain resulting from the direct activation of specialized sensory receptors (nociceptors) by noxious (potentially tissue-damaging) stimuli (thermal, mechanical, chemical).

Nociceptors

Free nerve endings of primary afferent neurons that detect and transmit noxious information from the periphery to the central nervous system.

A-delta fibers

Myelinated, fast-conducting fibers responsible for transmitting 'first pain' (sharp, pricking, well-localized sensation).

C fibers

Unmyelinated, slow-conducting fibers responsible for transmitting 'second pain' (dull, aching, throbbing, poorly localized).

Congenital Insensitivity to Pain with Anhidrosis (CIPA)

A rare genetic mutation causing an inability to feel pain and sweat, leading to severe self-inflicted injuries and poor survival rates.

Inflammatory Pain

Pain arising in response to tissue injury, infection, or inflammation, involving chemical mediators that sensitize the pain system (e.g., prostaglandins, bradykinin, cytokines).

Peripheral Sensitization

A process where inflammatory molecules lower the activation threshold of peripheral nociceptors and increase their responsiveness to stimuli.

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

Drugs (e.g., ibuprofen, aspirin) that reduce inflammatory pain by inhibiting cyclooxygenase (COX) enzymes, thereby reducing prostaglandin production.

Pathological Pain (Chronic Pain)

Persistent or recurrent pain for more than 3 months, beyond expected healing, representing maladaptive plasticity of the nervous system where the pain itself has become a disease entity.

Central Sensitization

A key mechanism in pathological pain characterized by increased excitability of neurons in the spinal cord and brain involved in pain processing, leading to exaggerated responses and expanded receptive fields.

Allodynia

A sensation of pain in response to a normally non-painful (non-noxious) stimulus (e.g., light touch on sunburned skin).

Hyperalgesia

An enhanced or exaggerated sensation of pain in response to a noxious stimulus that would normally cause pain (e.g., a mild cut feeling intensely painful).

Neuropathic Pain

Pain caused by a lesion or disease within the somatosensory nervous system itself (peripheral or central), characterized by burning, shooting, electric shock-like sensations.

Mixed Pain

Pain involving identifiable components of both inflammatory (or nociceptive) and neuropathic pain mechanisms (e.g., chronic lower back pain, cancer pain).

Idiopathic Pain

Pain with an unknown cause, where no specific underlying pathology can be identified despite thorough investigation.

Local Anesthetics (LAs)

Drugs that reversibly block nerve impulse conduction by inhibiting the influx of sodium ions (Na^+) through voltage-gated sodium channels in the neuronal membrane, preventing pain signals from reaching the brain.