How is neuropathic pain different from nociceptive pain?
It does not require activation of periphreal nociceptors to experience it.
It is also caused by lesions in the somatosensory system (neural) rather than tissue insult at sites of peripheral nociceptors.
What cells mantain the sensation of pain?
Cells supportive of the nerve fiber cells
Direct nerve fiber damage may also cause increased pain (release of bradykinins, etc..)
What is the definition of chronic pain?
Pain that persists beyond 3-6 months or significantly beyond normal healing time
What sort of pain are opiates great for? Not so great for?
Acute pain and end-of-life chronic pain
Not so good for chonic pain in younger pts (high addiction risk)
Between acute and chronic pain, which serves a purpose?
Acute pain lets us respond to the painful stimuli appropriately
Chronic pain has no physiological purpose
What does Substance P cause?
Neurogenic inflammation (heat, redness, swelling)
How does Substance P promote inflammation?
It induces the release of histamine by mast cells and causes local edema
Where does the first synapse between nociceptors and the CNS occur and what happens here (think transmitters)?
First synapse occurs at the dorsal horn of the spinal cord
Substance P and glutamate activate post-synaptic glutamatergic and NMDA receptors
Difference between central sensitization and peripheral sensitization
Both make the wound site and sites around the wound more painful (in a persistant manner)
However, peripheral sensitization is immediate while central sensitization is delayed by minutes
Describe secondary hyperplagia.
Phenomenon in which localized damage increases the local pain receptor field due to central sensitization
It explains the exagerrated nociceptor response after initial injury
What are the key features of neuropathic pain?
Sensory loss + paradoxical hypersensitivity
Characterized by spontaneous pain, dysesthesia, hypersenstivity
What is a neuroma?
An entanglement of nerve fibers that result from a cut nerve
The truncated nerve will try to regenerate itself, but due to lack of direction, this results in a neuroma.
Fibers in the neuroma have abberrant sodium channels that are more likely to fire! (hyperalgesia)
What signs are seen in neuropathic pain but rarely or never in inflammatory pain?
Cold allodynia (cold sensation causes pain)
Paroxysms (same stimulus produces increasing amount of pain)
Sensory or motor deficits in damaged nerve territory
There is no simple continuum from acute to chronic pain that correlates with duration or intensity of peripheral injury. T/F?
What happens when there is a prolonged interruption of the nerve contact point with its target?
Death of small unmyelinated neurons (excitotoxicity)
Death of inhibitory interneurons
Cortical changes in gray matter
Who are the main prescibers of opioid analgesics? (Top 3)
Primary Care Providers (PCP)
Dentists (top for ages 10-19)
America uses how much of the world's production of opiates? hydrocodone? illicit drugs?
80%, 99%, 66%
Are opioids effective for treating chronic pain?
Not according to many studies presented by Dr. Hayek (Excludes tramadol)
Physical dependence in opiates only occurs with high doses over months. T/F?
What is the most common side effect, occurring in 40-95% of all patients on opiates?
Does opioids help sleep?
No, they decrease total sleep time, REM sleep, delta sleep, etc..
Opioids have been shown to be immunosuppressive except for these two exceptions:
How does opiates induce hypogonadism?
What is hypogonadism characterized by?
Opioids bind in the hypothalamus and ultimately decreases release of LH and FSH.
Signs/symptoms: decreased libido, fatigue, depression, loss of muscle mass, infertility, erectile dysfunction, abnormal menses, osteoperosis
How do opioids exert its addicting qualities in the brain?
They inhibit release of GABA (in VTA/ventral tegmental area of midbrain)
This disinhibits dopaminergic neurons, flooding the nucleus accumbens with dopamine (reinforcement of rewards system)
Withdrawal symptoms indicate tolerance and addiction. T/F/partially T?
What are the ABCDE signs of addiction?
Unable to Abstain
Unable to control Behavior
Diminished recognition of problems
What are the 4 C's of addiction?
loss of control
ignoring negative consequences
State in which pt displays drug-seeking behavior due to untreated/poorly treated condition (resolves when treated)
Risk factors for opioid abuse include..
Fam hx of drug abuse
Hx of sexual abuse
Hx of mental illness
Unrealistic expectations of opioid treatment
What does current research suggest about the efficacy of NSAIDs in treating neuropathic pain?
There is little evidence to show its efficacy in neuropathic pain.
Some efficacy was shown, however, in diabetic neuropathy and post-herpes neuralgia.
Which kinds of antidepressants were found to be consistently more effective than placebo in treating neuropathic pain?
(they inhibit reuptake of NTs)
Results tempered by numerous side effects though
Tramadol is a cross between...
Tramadol is great for....
What side effects does tramadol not have that makes it a good treatment option?
-Morphine and Serotonin+NE inhibitor
-Neuropathic pain + good for nociceptive pain
-Tramadol does not cause end-organ damage AND is low risk for abuse
There is a strong correlation between plasma levels of antidepressants and pain relief. T/F?
How is Tramadol's affinity for mu receptors compared to morphine?
This results in a relative potency of _(Fraction)_ that of morphine
1/20 to 1/5
The enhanced analgesic effect of tramadol is most likely due to..
Inhibition of NE and 5HT reuptake in the CNS
Usual dose of tramadol is..
200-400 mg PO
Lidoderm patches. What's in it and what kind of patients are most likely to benefit from it the most?
5% Lidocaine, 700 mg
Pts experiencing allodynia (pain from non-pain sensations)
Note: almost no side effects
Which anticonvulsants have some efficacy in pain relief?
Topirimate, Gabapentin, Pregabalin
Note: gabapentin and pregabalin have very similar action mechanisms - Ca channel mod (gabapentin is more gradually release, pregabalin is more linear release)
What is Dr. Hayek's suggested algorithm for treating chronic pain?
Pregabalin/Gabapentin/Lidocain Patch (1st line)
Antidepressants (2nd line)
Opioids (3rd line)
What is the best kind of therapy for neuropathic pain management?
Combination therapy tailored to each individual pt