The document discusses various options for treating pain, including nonopioid analgesics like acetaminophen and NSAIDs which are effective for mild to moderate pain. Opioid analgesics are also discussed as options for moderate to severe pain. Adjuvant drugs like gabapentin, pregabalin, and certain antidepressants can help treat neuropathic pain. Neural blockade techniques like epidural analgesia and neuroablation provide pain relief through interrupting nociceptive pathways. Neuromodulation methods like TENS, spinal cord stimulation, and dorsal root ganglion stimulation may decrease pain through activating endogenous pain modulation.

1. DEPARTMENT OF NEUROLOGY
HEAD OF THE DEPARTMENT
Nehrych Tetyana , MD, PhD, Dr. Med. Sci. Prof.
Name : Mohamed Mahmoud Abbass
Group : 7th
Course : 4th

2. Analgesic
Nonopioid and opioid analgesics are the main drugs
used to treat pain.
Antidepressants, anticonvulsants, and other CNS-
active drugs may also be used for chronic or
neuropathic pain and are first-line therapy for some
conditions. Neuraxial infusion, nerve stimulation,
injection therapies, and neural blockade can help
selected patients.

3. Nonopioid Analgesics
Acetaminophen and NSAIDs are often effective for
mild to moderate pain
Acetaminophen has no anti-inflammatory or
antiplatelet effects and does not cause gastric
irritation.

4. Nonopioid Analgesics
NSAIDs include nonselective COX (COX-1 and COX-2)
inhibitors and selective COX-2 inhibitors (coxibs); all
are effective analgesics. Aspirin is the least
expensive but has prolonged antiplatelet effects.
Coxibs have lowest risk of ulcer formation and GI
upset. However, when a coxib is used with low-
dose aspirin, it may have no GI benefit over other
NSAIDs.

5. Nonopioid Analgesics
Inhibition of COX-2, which occurs with both
nonselective COX inhibitors and coxibs, has a
prothrombotic effect that can increase risk of MI,
stroke, and claudication. This effect appears to be
drug-related, as well as dose- and duration-related.
Although there is some evidence that the risk is
very low with some of the nonselective COX
inhibitors (eg, ibuprofen, naproxen) and coxibs
(celecoxib).

6. Nonopioid Analgesics
If an NSAID is likely to be used only short-term,
significant adverse effects are unlikely, regardless of
the drug used. Some clinicians use a coxib first
whenever therapy is likely to be long-term (e.g,
months) because the risk of GI adverse effects is
lower; others limit coxib use to patients
predisposed to GI adverse effects (eg, the elderly,
patients taking corticosteroids, those with a history
of peptic ulcer disease or GI upset due to other
NSAIDs).

7. Nonopioid Analgesics
If initial recommended doses provide inadequate
analgesia, a higher dose is given, up to the
conventional safe maximum dose. If analgesia
remains inadequate, the drug should be stopped. If
pain is not severe, another NSAID may be tried
because response varies from drug to drug. It is
prudent during long-term NSAID therapy to monitor
for occult blood in stool and changes in CBC,
electrolytes, and hepatic and renal function.

8. Topical NSAIDs may be applied directly to the painful
region for disorders such as osteoarthritis and
minor sprains, strains, and contusions. A 1.5%
solution of diclofenac has been shown to effectively
treat pain and limited joint function caused by
osteoarthritis of the knees; dose is 40 drops (1.2
mL) applied qid to each affected knee. Other
topical diclofenac formulations that may be useful
for local pain relief include a patch (applied bid over
the affected area) or a 1% gel (2 g qid for the upper
extremities or 4 g qid for the lower extremities).

10. Nonopioid Analgesics

11. Opioid Analgesics
“Opioid” is a generic term for natural or synthetic
substances that bind to specific opioid receptors in
the CNS, producing an agonist action.
Opioids are also called narcotics
a term originally used to refer to any psychoactive
substance that induces sleep. Opioids have both
analgesic and sleep-inducing effects, but the two
effects are distinct from each other.

12. Opioid Analgesics
Some opioids used for analgesia have both agonist
and antagonist actions. Potential for abuse among
those with a known history of abuse or addiction
may be lower with agonist-antagonists than with
pure agonists, but agonist-antagonist drugs have a
ceiling effect for analgesia and induce a withdrawal
syndrome in patients already physically dependent
on opioids.

13. Opioid Analgesics
In general, acute pain is best treated with short-acting
(immediate-release) pure agonist drugs at the
lowest effective dosage possible and for a short
time; CDC guidelines recommend 3 to 7 days.
Clinicians should reevaluate patients before re-
prescribing opioids for acute pain syndromes. For
acute pain, using opioids at higher doses and/or for
a longer time, increases the risk of needing long-
term opioid therapy and of having opioid adverse
effects.

14. Opioid Analgesics
Opioid agonists in combination products for moderate
pain
• Codeine
Oral: 30–60 mg q 4 h
0.5–1 mg/kg
Less potent than morphine
• Hydrocodone
Oral: 5–10 mg q 4–6 h
0.135 mg/kg
More potent than codeine

15. Opioid agonists for moderate-to-severe pain

17. Opioid misuse, diversion, and abuse
• Opioid misuse may be intentional or unintentional.
It includes any use that contradicts medical advice
or deviates from what is prescribed.
• Diversion involves selling or giving a prescribed
drug to others.
• Abuse refers to recreational or nontherapeutic use
(eg, euphoria, other psychotropic effects).
• Up to one third of patients taking long-term opioids
for chronic pain may misuse prescribed opioids or
may abuse them.

18. Addiction, typically marked by impaired control and
craving, refers to compulsive use despite harm and
negative consequences. Some definitions of
addiction include tolerance (an increasingly higher
dose is required to maintain the same level of
analgesia and efficacy over time) and withdrawal
(discontinuation of the drug or a significant
decrease in the dose causing withdrawal
symptoms).

19. Opioid antagonists
Naloxone acts in < 1 min when given IV and slightly less rapidly when
given IM. It can also be given sublingually or endotracheally.
Duration of action is about 60 to 120 min. However, opioid-induced
respiratory depression usually lasts longer than the duration of
antagonism; thus, repeated doses of naloxone and close monitoring
are necessary.
The dose for acute opioid overdosage is 0.4 mg IV q 2 to 3 min prn. If
repeated doses are necessary, the dose can be increased (to a
maximum of 2 mg IV per dose). If there is no response after 10 mg
has been given, the diagnosis of opioid toxicity should be
reconsidered.

20. Opioid antagonists
• Nalmefene is similar to naloxone, but its duration of
action is about 4 to 8 h. Nalmefene is occasionally
used to ensure prolonged opioid reversal.
• Naltrexone, an orally bioavailable opioid antagonist,
is given as adjunctive therapy in opioid and alcohol
addiction. It is long-acting and generally well-
tolerated.

21. Adjuvant Analgesic Drugs
Many drugs are used as adjuvant analgesics, including
anticonvulsants (eg, gabapentin, pregabalin),
antidepressants
(eg,tricyclics, duloxetine, venlafaxine, bupropion),
and many others.
These drugs have many uses, most notably to relieve
pain with a neuropathic component.

22. Adjuvant Analgesic Drugs
Gabapentin is the most widely used drug for such
purposes. For effective analgesia, the dose should
usually be > 600 mg po tid, and many patients need
a higher dose. Maximum dosage is usually
considered 1200 mg po tid.
Gabapentin is widely used for neuropathic
pain and headache syndromes.

23. Adjuvant Analgesic Drugs
Pregabalin is similar to gabapentin but has more
stable pharmacokinetics; bid dosing is as efficacious
as tid dosing, so compliance is better. The dosing
goal is at least 300 mg/day po (eg, a starting dose of
75 mg bid, increased to 150 mg bid within 1 wk).
Neuropathic pain syndromes may require up to 600
mg/day.
Pregabalin is effective for neuropathic pain (including
central pain due to spinal cord injury)

24. Adjuvant Analgesic Drugs
tricyclic antidepressants
(amitriptyline, nortriptyline, desipramine), the
primary mechanism of action is blocking the
reuptake of serotonin and norepinephrine.
Analgesic doses (75 to 150 mg po once/day) are
usually insufficient to treat depression or anxiety.
Tricyclic antidepressants are effective for neuropathic
pain, myofascial pain syndromes, some central
neuropathic pain syndromes, visceral pain
syndromes, and headache syndromes.

25. Adjuvant Analgesic Drugs
• Duloxetine is a mixed mechanism (serotonin
and norepinephrine) reuptake inhibitor, which
appears to be effective for diabetic neuropathic
pain, fibromyalgia, chronic musculoskeletal pain
(including low back pain), and chemotherapy-
induced neuropathy.

30. Neural Blockade
Local anesthetic drugs (eg, lidocaine) can be given IV,
intrathecally, intrapleurally, transdermally,
subcutaneously, or epidurally. Epidural analgesia
using local anesthetics or opioids is particularly
useful for some types of postoperative pain.
Long-term epidural drug administration is occasionally
used for patients with localized pain and a short life
expectancy. Generally, for long-term neuraxial
infusion, an intrathecal route via an implanted
pump is preferred.

31. Neural Blockade
Neuroablation involves interrupting a nociceptive
pathway surgically or using radiofrequency
energy to produce a lesion. The procedure is used
mainly for cancer pain. Somatic pain is more
responsive than visceral pain.
Neuroablation of the ascending spinothalamic tract
(cordotomy) is usually used; it provides relief for
several years, although numbness and
dysesthesias develop. Neuroablation of the
dorsal roots (rhizotomy) is used when a specific
dermatome can be identified.

32. Neuromodulation
Stimulation of neural tissues may decrease pain,
presumably by activating endogenous pain
modulatory pathways. The most commonly used
noninvasive method is transcutaneous electrical
nerve stimulation (TENS), which applies a small
current to the skin.
Evidence supports treatment of certain types
of neuropathic pain (eg, chronic leg pain after
spine surgery) using an electrode placed
epidurally to stimulate the spinal cord.

33. Neuromodulation
Advances in electrical stimulation paradigms have
improved the efficacy of neuromodulation
techniques.
New techniques include
• High-frequency stimulation
• Dorsal root ganglion stimulation

34. Neuromodulation
• High-frequency stimulation is efficacious for
neuropathic limb pain. Efficacy is similar to that of
traditional neuromodulation techniques, but
evidence suggests that it may also be efficacious for
axial spine pain, which is not effectively treated
with traditional neuromodulation techniques.
• Dorsal root ganglion stimulation is a more focused
neuromodulatory treatment; it targets localized
neuropathic pain within limited dermatomes.

35. Thanks