Pain

NSC4354 Lecture 3: Pain

tissue destruction

Pain involves __ ___ induced by:

– Thermal or chemical stimuli

– Mechanical force

poorly localized

Pain reception is ___ ___ (as is temperature)

emotional component

Pain involves an ___ ___ that can be used to modify the magnitude of pain perception

Nociception

The neural encoding and processing of noxious stimuli

Nociceptors

Sensory receptors that detect signals from damaged tissue (or the threat of damage)

→ Free (bare) nerve endings found in the skin, muscle, joints, bone and viscera.

free nerve endings

Peripheral nociceptive axons terminate in ___ ___ ___

Aδ and C fibers

The small fibers on which nociceptors are found on

They conduct relatively slowly

Aδ fibers

Respond to intense mechanical and thermal stimuli (2 types)

(pain and temperature)

Type I Aδ fibers

Aδ fibers sensitive to mechanical, not thermal stimuli

Respond to dangerously intense mechanical and chemical stimulation and have high heat thresholds.

Type II Aδ fibers

Aδ fibers sensitive to thermal, not mechanical

Have low heat thresholds, but high thresholds for mechanical stimulation.

C fibers

They are polymodal → respond equally to thermal, mechanical, and chemical stimuli

(pain, temperature, and itch)

somatosensation

Pain is processed separately from ____

do not

Peripheral axons responsible for normal stimulation (do/do not?) increase their frequency in response to painful stimuli.

does not

Direct stimulation of large fibers (Ia, II, Aβ) (does/does not?) produce pain

high intensities

In contrast, nociceptive afferents only fire when stimuli reach ___ ___.

Fast pain

• Myelinated (A delta) fibers

• Sharp pain

• “First pain”

Slow pain

• Unmyelinated C fibers

• Dull, burning quality

• Longer-lasting

• “Second pain”

dorsal column-medial lemniscus system

The touch pathway

anterolateral system

The pain pathway

First order neurons

Dorsal root ganglia (pathway in Lissauer’s tract)

Second order neurons

Located in Rexed’s laminae I, II and V of spinal cord

- Layers 1 and 5 contain projection neurons to brainstem and thalamus

- Layer 2 contains interneurons

• C fibers terminate in laminae I and II

• Aδ fibers terminate in laminae I and V

anterolateral tract

Projections from second order neurons cross midline and give rise to the ___ ___ and ascend to the brainstem and thalamus

dissociated sensory loss

unilateral spinal cord lesions cause this and it is a signature of spinal cord lesions

• contralateral → reduction in pain and temperature sensation

• ipsilateral → reduction in touch, pressure, vibration and proprioception

Anterolateral pathway

Pain from the body

• First order neurons synapse in dorsal horn

• Second order neurons decussate and ascend to brainstem and VPL thalamus in the spinothalamic tract

• Third order neurons ascend to somatosensory cortex

Trigeminothalamic tract

face/head/teeth pain

• First order neurons located in the trigeminal ganglion descend to the medulla and synapse on the spinal trigeminal nucleus

• Second order neurons decussate and ascend to brainstem and VPM thalamus in the trigeminothalamic tract

• Third order neurons ascend to somatosensory cortex

Visceral pain pathway

pain from visceral organs of the pelvis, abdomen, and thorax

• First order neurons located in the dorsal root ganglion enter the spinal cord and synapse:

– in the dorsal horn

– In the intermediate gray region of the spinal cord (near central canal)

• Intermediate gray region second order neurons ascend through the dorsal columns VERY near the midline to the dorsal column nuclei (gracile nucleus)

• Third order neurons cross the midline and ascend to the VPL thalamus

midline myelotomy

Surgical transection of axons in medial dorsal column brings pain relief from visceral cancers in abdomen and pelvis

Referred pain

visceral pain misperceived as cutaneous pain

Angina

poor perfusion of heart muscle perceived as pain in shoulder, chest, or arm/hand

Multimodal lamina 5 neurons

Neurons that integrate both nociceptive and non-nociceptive inputs

Sensory discriminative aspects of pain

The location, intensity, or quality of pain

Affective motivation aspects

The unpleasant feeling, fear, and/or anxiety of pain

Context-specificity

The situation/circumstance which you are experiencing your pain

Ex. Soldiers suffering from severe battle wounds often experience little or no pain

Placebo effect

• Physiological response following administration of a pharmacologically inert “remedy”

• Med students given “sedative” or “stimulant”

• Postoperative wound pain improved after saline injection

Endogenous analgesia system

A natural pain-relieving system in the body that includes endorphins, enkephalins, and other molecule

Periaqueductal gray

Stimulation of this area in the midbrain relieves pain and inhibits the activity of nociceptive projection neurons in the dorsal horn of the spinal cord

Controls nociceptive neurons in dorsal spinal horn through 4 nuclei in the brainstem: Parabrachial nucleus, Medullary reticular formation, Locus coeruleus, Raphe nuclei

→These centers employ a wealth of different neurotransmitters that can exert both facilitatory and inhibitory effects on the activity of dorsal horn neurons

Gate theory of pain

Local interactions in the spinal cord modulate pain perception

• The flow of nociceptive information (Aδ and C fibers) through the spinal cord is modulated (reduced) by simultaneous activity in the large myelinated “touch” fibers

→ rubbing the skin after stubbing your toe

Endogenous opioids

Peptides that bind to the same postsynaptic receptors as opium

3 groups of ____ ____ receptor ligands:

• Endorphins (

• Enkephalins

• Dynorphins

Analgesic

(of a drug) acting to relieve pain

Includes morphine, heroin, and synthetic opiates such as methadone and fentanyl

Enkephalins

_____, endorphins and dynorphins are released in the periaqueductal gray

→ Source of pain-modulating pathways to the dorsal horn in spinal cord

Also released directly in the spinal cord to blunt the effects of nociceptor activation

Phantom limb pain

• Following amputation of a limb, tingling or burning sensation in the missing part

→ Problematic to treat because of the widespread nature of central pain processing and cortical reorganization after amputation

Transient receptor potential (TRP) channels

A family of receptors sensitive to different ranges of heat and cold