Overview of Pain Management

Question 1

How to treat acute, mild/moderate nociceptive pain

Answer 1

Non-opioids

+/- opioids

Question 2

How to treat acute, mod-severe nociceptive pain

Answer 2

Opioids
+/- Multi-modal analgesia
(LA, ketamine, clondine, non-opioids)

Question 3

What is nociceptive pain?

Answer 3

“Normal” pain resulting from activation of nociceptive nerve fibers

Somatic pain or visceral pain

Question 4

What is neuropathic pain?

Answer 4

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

Question 5

Treatment for mild-moderate chronic neuropathic pain

Answer 5

Non-opioids +/- adjuvants (decrease central sensitization, decr peripheral sensitization, increased descending inhibition)

Question 6

Treatments for severe chronic pain

Answer 6

Tramadol, buprenorphine, other opioids (esp with cancer)

Question 7

What is the most important in central sensitization?

Answer 7

NMDA receptor (responds to glutamate)
Blocked with ketamine

Question 8

What is not used in actue pain management?

Answer 8

SNRIs (adjuvants not usually used)

Ketamine IS!

Question 9

What is multimodal analgesia?

Answer 9

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

Question 10

NSAIDs and COX-2 Inhibitors

Answer 10

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)

Question 11

What drugs decrease the transduction of acute nociceptive pain?

Answer 11

NSAIDs (ibuprofen): inhibition of COX-2 and PG synthesis → reducing peripheral and central sensitization

Question 12

What drugs decrease the transmission of acute nociceptive pain?

Answer 12

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

Question 13

What drugs modulate the transmission of acute nociceptive pain?

Answer 13

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

Question 14

What is the main contributing factor to the onset of action of opioids?

Answer 14

Route of administration and lipid-solubility

Question 15

What is the main contributing factor to the duration of action of opioids?

Answer 15

Formulation of opioid (immediate-release, sustained-release, etc.)

Question 16

Mechanisms of neuropathic pain

Answer 16

Peripheral sensitization, central sensitization, and ectopic activity

Question 17

Peripheral sensitization as a mechanism of neuropathic pain and how to block it

Answer 17

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

Question 18

Central sensitization as a mechanism of neuropathic pain

and how to block it

Answer 18

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

Question 19

Ectopic activity as a mechanism of neuropathic pain and how to block it

Answer 19

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

Question 20

Adjuvant medications

Answer 20

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

Question 21

Drugs that enhance the Descending Inhibitory pathway from the brain

Answer 21

Activation of opioid receptors: opioid analgesics, tramadol

Block of NE-5HT reuptake: antidepressants-TCAD-SNRI-SSRI