The Neurophysiology of Pain

November 13, 2012

What is Pain?

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
International Association for the Study of Pain1

Types of Pain1: Classification by Duration

Acute vs chronic1
Acute pain
An unpleasant experience with emotional, cognitive, and sensory features, resulting from tissue trauma Usually associated with significant, observable tissue pathology Resolves with healing of causative injury Protective biological function to protect against further injury; protective reflexes include withdrawal, muscle spasm, and autonomic reactions

Chronic pain
Pain lasting beyond expected recovery period and identifiable pathology insufficient to explain the pain state Disrupts sleep and normal activities of living Does not serve a protective, adaptive function

Types of Pain2: Classification by Etiology

Nociceptive vs neuropathic1
Nociceptive pain
Results from normal function of the nervous system Caused when a noxious stimulus (eg, trauma, inflammation, infection) activates A-delta and C nociceptors

Neuropathic pain
Abnormal nociceptive signaling caused by an impairment of the nervous system Serves no functional or adaptive purpose Causes and examples

Visceral pain: originates in internal organs Somatic pain: originates in skin, muscle, skeletal structures

Metabolic: diabetic neuropathy Infectious: herpes zoster Trauma: nerve entrapment

The Neurophysiology of Pain1

Nociception: process by which information about tissue damage reaches the central nervous system Transduction Transmission Perception Modulation

Pain Transduction2
Nociceptor = pain receptor: specialized receptor for detecting tissue injury/damage Two classes of nociceptive afferent fibers
Drawing of A-delta axon
Type Caliber A-delta Small diameter, thinly myelinated Thermal & high-threshold mechanical

Drawing of C axon
C Small diameter, unmyelinated Polymodal: high-intensity mechanical, chemical, heat, cold 0.5-2 More prolonged sensation of dull pain

Stimuli Conduction velocity (meters/sec) Effect of activation

5-30

Short, sharp, prickling pain

Pain Transduction (continued)

Nociceptors do not spontaneously depolarize: they send impulses (action potentials) only when stimulated No specialized pain receptors
The receptor region of the nociceptor is the free terminal of the axon

Ion channels in nerve terminal open in response to noxious stimuli, initiating an action potential, the pain signal2 Peripheral sensitization: local tissue injury with release of inflammatory mediators can enhance nociceptor response2,3

Pain Transmission
Nociceptors (primary sensory afferents) have cell body in dorsal root ganglia; synapse to second-order neurons in dorsal horn of spinal cord Pain impulses can trigger a withdrawal reflex via connections to motor neurons in the spinal cord3 Impulses ascend to brain via various ascending tracts1,3
Spinothalamic tract > thalamus Spinohypothalamic tract > hypothalamus Spinomesencephalic tract > mesencephalon Spinoreticular tract > reticular formation of brainstem

Pain Perception
Perception of and reaction to pain are influenced by social and environmental cues, as well as by cultural norms and personal experience1

Both cortical and limbic systems are involved in conscious awareness (perception) of pain1
Recognition of location, intensity, and quality of pain is mediated by processing of signals from the spinothalamic tract > thalamus > somatosensory cortex1 Pain information processing in the brainstem, midbrain, and limbic system appear to mediate affective, motivational, and behavioral responses to painful stimuli3

Pain Modulation
Gate control theory advanced by Melzack and Wall in 1965 focused on descending pathways from the brain to the spinal cord that inhibit pain signaling4 Current view: signals originating in the brain can both inhibit and facilitate pain signal transmission3 Neurotransmitters involved in these pathways include
Endogenous opiates (enkephalins, dynorphins, beta-endorphins)2 Serotonin Norepinephrine

References
1. National Pharmaceutical Council and Joint Commission on Accreditation of Healthcare Organizations. Pain: Current Understanding of Assessment, Management, and Treatments. Reston, VA: National Pharmaceutical Council; 2001. Carver A. Pain. In: Dale DC, Federman DD, eds. ACP Medicine. New York, NY: WebMD; 2005:1-18. Hudspith MJ, Siddall PJ, Munglani R. Physiology of pain. In: Hemming HC, Hopkins PM, eds. Foundations of Anesthesia. 2nd ed. London, UK: Mosby; 2006:267-285. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150(3699):971-979.

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