How to treat acute, mild/moderate nociceptive pain
How to treat acute, mod-severe nociceptive pain
+/- Multi-modal analgesia
(LA, ketamine, clondine, non-opioids)
What is nociceptive pain?
“Normal” pain resulting from activation of nociceptive nerve fibers
Somatic pain or visceral pain
What is neuropathic pain?
Distinct from nociceptive pain - persists and has become disengaged from noxious stimuli or the healing process
Result of nerve damage. Syndromes include: diabetic neuropathy, postherpetic neuralgia
Abnormal operation of the nervous system. Syndromes include: fibromyalgia, irritable bowel syndrome, tension type headache
Described as burning, tingling, shock-like or shooting
Treatment for mild-moderate chronic neuropathic pain
Non-opioids +/- adjuvants (decrease central sensitization, decr peripheral sensitization, increased descending inhibition)
Treatments for severe chronic pain
Tramadol, buprenorphine, other opioids (esp with cancer)
What is the most important in central sensitization?
NMDA receptor (responds to glutamate) Blocked with ketamine
What is not used in actue pain management?
SNRIs (adjuvants not usually used)
What is multimodal analgesia?
Use of multiple classes of analgesics acting via different pathways TARGETS
Benefits of combining other agents with opioids
Greater analgesic efficacy from synergistic actions of agents with different mechanisms
Synergism between agents allows use of lower doses (“opioid-sparing”) limiting dose-related side effects
NSAIDs and COX-2 Inhibitors
Inhibitors of COX-2 - PG synthesis in inflammatory cascade
blocks pain sensitization at both peripheral and CNS sites
Consistently shown to reduce post-op opioid requirements by 20-40% (multiple types of surgeries)
What drugs decrease the transduction of acute nociceptive pain?
NSAIDs (ibuprofen): inhibition of COX-2 and PG synthesis → reducing peripheral and central sensitization
What drugs decrease the transmission of acute nociceptive pain?
Local anesthetics (lidocaine): block of voltage-sensitive sodium channels (VSSC) → reducing nociceptive stimuli action potential
NMDA receptor antagonists (ketamine): block glutamate receptor depolarization at 2nd order neuron → decreased transmission of nociceptive stimuli
What drugs modulate the transmission of acute nociceptive pain?
μ-opioid receptor agonists (morphine): block glutamate-substance P release from primary neuron plus hyperpolarize 2nd order neuron → attenuation of afferent-evoked excitation of 2nd order neuron → decreased transmission of nociceptive stimuli
α2-adrenergic receptor agonists (clonidine): block glutamate-substance P release from primary neuron → attenuation of afferent-evoked excitation of 2nd order neuron → decreased transmission of nociceptive stimuli
What is the main contributing factor to the onset of action of opioids?
Route of administration and lipid-solubility
What is the main contributing factor to the duration of action of opioids?
Formulation of opioid (immediate-release, sustained-release, etc.)
Mechanisms of neuropathic pain
Peripheral sensitization, central sensitization, and ectopic activity
Peripheral sensitization as a mechanism of neuropathic pain and how to block it
Tissue inflammation may change chemical environment at terminals of nociceptor. Damaged cells release-synthesize proinflammatory mediators that can directly activate the terminal and produce pain or render the terminal hypersensitive to subsequent stimuli
Block it with NSAIDs and LA
Central sensitization as a mechanism of neuropathic pain
and how to block it
NMDA receptor is central to the amplification of synaptic transfer from terminal to dorsal horn neurons. Initial sensitization is activity dependent, then later sustained by transcriptional changes (via COX-2, BDNF, substance P, NK1)
NMDA receptor antagonists and alpha 2 agonist
Ectopic activity as a mechanism of neuropathic pain and how to block it
Increased excitability of injured sensory neurons can generate pacemaker-like ectopic discharges that result in sensory inflow that is independent of any peripheral stimuli.
Block with LA
Agents that enhance analgesic efficacy, treat concurrent symptoms that exacerbate pain, and/or provide independent analgesic activity for specific types of pain as below.
Used for chronic pain usually
- TCADs: Diabetic neuropathy, migraine, low back pain, postherpetic neuralgia
- SNRIs: Fibromyalgia
- Anticonvulsants: Spinal cord injury, trigeminal neuralgia, diabetic neuropathy
- Local Anesthetic (topical): Post herpetic neuralgia, allodynia if pain localized
Drugs that enhance the Descending Inhibitory pathway from the brain
Activation of opioid receptors: opioid analgesics, tramadol
Block of NE-5HT reuptake: antidepressants-TCAD-SNRI-SSRI