Pain Management Nursing Exam

This chapter walks through transduction, transmission, perception and modulation, the chemical mediators and nerve fibers involved, and the drugs and nursing interventions that act at each step. ANCC likes questions that ask where a therapy works or why combining agents is more effective.

Transduction is the conversion of a noxious mechanical, thermal or chemical stimulus into an electrical signal at the peripheral nociceptor (free nerve ending). Tissue injury releases and attracts a chemical soup of mediators: prostaglandins, bradykinin, histamine, serotonin, substance P, potassium, hydrogen ions, ATP and inflammatory cytokines. These mediators directly activate nociceptors or lower their threshold. Prostaglandins, produced by cyclooxygenase (COX) enzymes from arachidonic acid, sensitize nociceptors to other mediators.

When the stimulus is strong enough, sodium channels open, the membrane depolarizes and an action potential begins.

Drugs and therapies acting at transduction:

• NSAIDs block COX-1 and COX-2, reducing prostaglandin production and inflammation.
• Corticosteroids reduce inflammatory mediator production.
• Local anesthetics (lidocaine, bupivacaine, ropivacaine) block voltage-gated sodium channels, preventing action potentials; they act at transduction when infiltrated into tissue and at transmission when placed around nerves.
• Topical agents such as lidocaine 5% patch and capsaicin (which depletes substance P and defunctionalizes nociceptor endings).
• Cold therapy reduces inflammation, edema and nerve conduction.
• Peripheral opioid receptors exist in inflamed tissue, which is one reason opioids can have some peripheral effect.

Transmission is the movement of the impulse from the periphery to the spinal cord and up to the brain. It occurs in three segments: along the peripheral nerve to the dorsal horn, across the synapse in the dorsal horn, and up ascending tracts to the brain.

Two primary afferent fibers carry nociceptive signals. A-delta fibers are thinly myelinated, fast-conducting fibers that carry sharp, well-localized "first pain," the quick sting that prompts withdrawal. C fibers are unmyelinated, slow-conducting fibers that carry dull, aching, burning, poorly localized "second pain," which lingers. A-beta fibers are large, heavily myelinated fibers that normally carry touch, pressure and vibration; they are central to gate control theory, and in sensitized states they can contribute to allodynia.

In the dorsal horn of the spinal cord (mainly the substantia gelatinosa, laminae I, II and V), primary afferent terminals release excitatory neurotransmitters, chiefly glutamate and substance P, along with calcitonin gene-related peptide (CGRP). These bind to AMPA, NMDA and neurokinin receptors on second-order neurons. The signal crosses to the opposite side and ascends mainly through the spinothalamic tract to the thalamus, which relays it to the cortex.

Drugs acting at transmission:

• Opioids bind mu, kappa and delta receptors in the dorsal horn (presynaptically reducing neurotransmitter release and postsynaptically hyperpolarizing second-order neurons) and in the brain.
• Local anesthetics in epidurals, spinals and peripheral nerve blocks block conduction along nerves.
• Gabapentin and pregabalin bind the alpha-2-delta subunit of voltage-gated calcium channels, reducing excitatory neurotransmitter release.
• Ketamine and methadone block NMDA receptors, reducing glutamate-driven amplification.
• Alpha-2 agonists such as clonidine (including epidural and intrathecal clonidine) reduce dorsal horn transmission.
• Ziconotide, given intrathecally, blocks N-type calcium channels.

Perception is the conscious recognition and interpretation of pain. It is the point at which nociception becomes pain. The somatosensory cortex identifies location, intensity and quality. The limbic system and anterior cingulate cortex add the emotional and unpleasant dimension, and the prefrontal cortex adds meaning, memory, expectations and evaluation. This is why fear, anxiety, depression, catastrophizing, past experience, culture and attention shape how much a stimulus hurts.

Interventions acting at perception include distraction, guided imagery, relaxation, music, hypnosis, cognitive-behavioral therapy, mindfulness, pain neuroscience education and the reassurance that comes from good preoperative teaching. Opioids also act in the brain, partly by changing the emotional response to pain (patients sometimes say "it still hurts but it doesn't bother me").

Modulation is the process by which the nervous system increases or decreases the nociceptive signal. The descending inhibitory pathway begins in the periaqueductal gray (PAG) of the midbrain and passes through the rostral ventromedial medulla (RVM) to the dorsal horn, where it dampens transmission. Its neurotransmitters include endogenous opioids (endorphins, enkephalins, dynorphins), serotonin, norepinephrine and gamma-aminobutyric acid (GABA). Modulation can also facilitate pain: descending facilitation contributes to chronic pain states.

Drugs that enhance descending inhibition:

• SNRIs (duloxetine, venlafaxine, milnacipran) and TCAs (amitriptyline, nortriptyline) block reuptake of serotonin and norepinephrine. Their analgesic effect is separate from their antidepressant effect and often occurs at lower doses.
• Tramadol and tapentadol combine mu-opioid agonism with norepinephrine (and for tramadol, serotonin) reuptake inhibition.
• Opioids mimic endogenous opioids at the PAG, RVM and dorsal horn.
• Alpha-2 agonists such as clonidine and dexmedetomidine act on descending noradrenergic pathways.

• Transduction converts a noxious stimulus to an electrical signal; NSAIDs, steroids, local anesthetics and capsaicin act here.
• A-delta fibers carry fast, sharp first pain; C fibers carry slow, dull second pain; A-beta fibers carry touch.
• In the dorsal horn, glutamate and substance P transmit the signal; opioids, gabapentinoids, ketamine and local anesthetics reduce transmission.
• Perception involves the somatosensory cortex for location and intensity and the limbic system for emotion; cognitive and behavioral therapies act here.
• Descending modulation from the PAG and RVM uses endogenous opioids, serotonin, norepinephrine and GABA; SNRIs, TCAs, tramadol and tapentadol enhance it.