This document discusses neuropathic pain, its causes, symptoms, and treatment options. It begins by defining neuropathic pain as pain resulting from damage or disease affecting the somatosensory nervous system, such as diabetic neuropathy or postherpetic neuralgia. Symptoms include abnormal sensations like tingling, burning, and pain from stimuli that are normally non-painful. Treatment options discussed include tricyclic antidepressants, gabapentin, pregabalin, serotonin-norepinephrine reuptake inhibitors, topical lidocaine, opioids, and emerging treatments like botulinum toxin, cannabinoids, spinal cord stimulation, and intrathecal drug delivery.

1. NEUROPATHIC PAIN
DR MOHAMMAD A.S. KAMIL
CONSULTANT NEUROLOGIST

2.  Neuropathic pain resulting directly from a
lesion or disease affecting the
somatosensory system.
 diabetic polyneuropathies, postherpetic
neuralgia, trigeminal neuralgia, and central
poststroke or spinal cord injury pain.
 Traumatic or postsurgical neuropathies and
painful radiculopathies are also common
conditions in the general population.

3.  Paresthesia are abnormal spontaneous or stimulus-
independent sensations, often described as tingling or
compared to a limb that has fallen "asleep.
 Dysesthesia refers to an unpleasant abnormal sensation
that can be spontaneous or evoked.
 allodynia to pain following contact by a normally non-
noxious stimulus.
 hyperalgesia to exaggerated pain from a noxious
stimulus
 Hyperpathia is a complex sensory experience
characterized by an abnormally painful reaction to a
stimulus, especially a repetitive stimulus, in a patient who
initially perceives the stimulus as less intense.

4. MAJOR MECHANISMS INVOLVED IN
NEUROPATHIC PAIN
Peripheral Mechanisms:
 Abnormal (ectopic) neuronal activity has been reported in primary
afferents and in the dorsal root ganglion and appears to be mainly
related to dysregulation of the synthesis or the functioning of
sodium channels (notably the tetrodotoxin resistant channels),
although potassium channels may also be involved.
 Nerve injury also induces upregulation of several receptor
proteins, including transient receptor potential vanilloid 1
(TRPV1).
TRPV1 is located on subtypes of peripheral nociceptive
endings and is physiologically activated by noxious heat, among
other stimuli.
After a nerve lesion, TRPV1 is upregulated in uninjured C
fibers and downregulated in injured nerve fibers.

5. CENTRAL MECHANISMS
 Several major types of modifications can induce pathologic
activation of central nociceptive neurons:
 1)modification of the modulatory controls of the transmission of
nociceptive messages;2) anatomic reorganization
(neuroplasticity) of the central nociceptive neurons and thus their
pathologic activation; 3)microglial activation; and 4) central
sensitization (hyperexcitability) of nociceptive neurons.
 Central sensitization probably depends critically on intracellular
changes induced by the activation of NMDA receptors or other
receptors (ie, glutamate metabotropic receptors) by excitatory
amino acids released by primary afferents.
 Because of the multiplicity of mechanisms, it is unlikely that NP is
related to only one mechanism.

6. CURRENT DRUG TREATMENT FOR NEUROPATHIC
PAIN .
Tricyclic antidepressants
 Nortriptyline ,Desipramine ,Amitriptyline
 Inhibition of reuptake of monoamines, block of
sodium channels, anticholinergic.
 Somnolence, anticholinergic effects, weight gain.
 Cardiac disease (ECG), glaucoma,prostatic
adenoma, seizure, use Desipramine of tramadol.
A: Diabetic neuropathy, postherpetic neuralgia
(PHN)
B: Spinal cord injury/central side effects poststroke
pain, traumatic nerve lesions, cancer neuropathic
pain

7. SEROTONIN NOREPINEPHRINE
REUPTAKE INHIBITORS
 Duloxetine ,Venlafaxine Inhibition of
serotonin and norepinephrine reuptake.
 Nausea
 (A: Diabetic neuropathy).

8. CALCIUM CHANNEL ALPHA-2-DELTA
LIGANDS
Gabapentin,Pregabalin
 Acts on alpha-2-delta subunit of voltage-gated calcium
channels, which decreases central sensitization.
 Sedation, dizziness, peripheral edema,weight gain.
 Reduce dosages in renal insufficiency.
 Gabapentin:A: Diabetic neuropathy, PHN,cancer
neuropathic pain
 B: Spinal cord injury pain No clinically significant drug
interactions, improvement of generalized anxiety and
sleep
 Pregabalin:A: Diabetic neuropathy, PHN, spinal cord
injury pain

9. TOPICAL LIDOCAINE
Lidocaine 5% plasters:
 Block of sodium channels
 Local erythema, itch, rash.
 No systemic side effects,potential effect on
allodynia.
A: PHN 1 to 3 patches/3 patches.

10.  Capsaicin patches 8%
 Transient receptor potential vanilloid 1
agonist
 Pain, erythema, elevated blood pressure due
to initial increase in pain.
 No systemic side effects, potential effects on
burning pain, itching, and allodynia.
 A: HIV neuropathy and PHN 1 to 4 patches
to cover the painful area, repeat every 3
months.

11. OPIOID AGONISTS
Tramadol
 Mu receptor agonist and inhibition of monoamine
reuptake
 Nausea and vomiting, constipation, dizziness,
somnolence.
 History of substance abuse, suicide risk, use of
antidepressants in elderly patients.
 Rapid onset of analgesic effect, effect on
inflammatory pain
 A: Diabetic neuropathy, phantom pain
 B: Spinal cord injury pain

12.  Morphine, oxycodone,methadone,
levorphanol
 Mu receptor agonists (oxycodone may also
cause k-receptor antagonism)
 Nausea and vomiting, constipation,
dizziness,somnolence.
 Rapid onset of analgesic effect,effect on
inflammatory pain
 A: Diabetic neuropathy, PHN, phantom pain

13. OTHER NEUROPATHIC PAIN
INDICATIONS
 pregabalin is now the drug of choice for SCI
pain.
 A Class I trial showed no superiority of
duloxetine over placebo on the primary outcome
of central pain due to stroke or SCI, but several
secondary outcomes, including allodynia to
brush and cold, favored duloxetine.
 Studies of gabapentin have found positive
results in Guillain-Barre´ syndrome and cancer
NP and discrepant results in phantom limb pain.

14.  Opioids and tramadol have been found to be
efficacious for phantom limb pain.
 amitriptyline has been found to be
efficacious for cancer neuropathic pain.
 A recent large-scale study using an
enrichment phase demonstrated no benefit
of pregabalin for lumbosacral radiculopathy.

15. EMERGING TREATMENTS FOR
NEUROPATHIC PAIN
 Botulinum Toxin Type A:
 Several lines of investigation have suggested that botulinum toxin
type A (BTX-A), a potent neurotoxin commonly used for the
treatment of focal muscle hyperactivity, may have analgesic
effects independent of its action on muscle tone, possibly by
acting on neurogenic inflammation.Such mechanisms may be
involved in some cases of peripheral NP.
 Three single-center RCTs reported the long-term efficacy of a
series of subcutaneous injections of BTX-A (from 100 to 200 U)
injected into the painful area among patients with
mononeuropathies (traumatic or related to herpes zoster) and
patients with diabetic PPNs.
 Interestingly, in these two studies, the onset of efficacy (about 1
week) and duration of effects (3 months) was remarkably similar.
 The drug had an excellent safety profile; patients reported only
pain during injection and no systemic side effects.

16. CANNABINOIDS
 The therapeutic potential of cannabinoids has been extensively
investigated in chronic pain following the discovery of
cannabinoid
receptors and their endogenous ligands.
 Oromucosal cannabinoids (2.7 mg delta- 9-
tetrahydrocannabinol/2.5 mg cannabidiol) are effective for
multiple sclerosis associated pain and for refractory peripheral NP
associated with allodynia.
 Adverse events include dizziness, dry mouth, sedation, fatigue,
gastrointestinal effects, and oral discomfort.
 cannabinoids are not recommended for patients with psychiatric
disorders.
 There is controversy with regard to tolerance and dependence
after long-term treatment.

17. STIMULATION TECHNIQUES AND
INTRATHECAL THERAPY
 Transcutaneous electrical nerve stimulation
(TENS) is commonly used for the treatment of
pain associated with peripheral neuropathies,
although the evidence level is moderate (Level
B).
 TENS can be proposed as a first-line treatment
for painful focal neuropathies.
 Interest in noninvasive brain stimulation
(notably transcranial magnetic stimulation) for
the treatment of NP is increasing.

18.  Spinal cord stimulation has been reported to
be efficacious in patients with failed back
surgery syndrome , and motor cortex
stimulation has been increasingly used for
the treatment of peripheral or central painful
neuropathic conditions.

19.  For refractory NP, opioids and local
anesthetics can be delivered intrathecally
and have shown some benefit, although no
Class I studies regarding their efficacy
specifically in NP have been reported.

20. First Line
 Gabapentin
 Tricyclic antidepressants
 Tramadol
 Duloxetine
 Pregabalin

21. Second Line
 Lamotrigine
 Carbamazepine
 Bupropion SR
 Venlafaxine XR
 Opiate analgesics

22. THANK YOU