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NEUROMODULATION
Dr VIKAS KUMAR DWIVEDI
Neurosurgery department
SGPGI
WHAT is Neuromodulation???
• Neuromodulation is the targeted release of a substance from a neuron that alters
the efficacy of synaptic transmission or the cellular properties of neuron
• It is the physiological process by which a given neuron uses one or more
neurotransmitters to regulate diverse populations
There is targeted delivery of a stimulus, such as electrical stimulation or chemical
agents to specific neurological sites in the body".
It is carried out to normalize – or modulate – nervous tissue function.
NEUROMODULATION Vs SYNAPTIC TRANSMISSION
NEUROMODULATION
• It occurs when a substance released
from one neuron alters the cellular or
synaptic properties of another neuron
• G protein coupled receptors
• slow
SYNAPTIC TRANSMISSION
• One presynaptic neuron directly
influnces a single postsynaptics
partner
• Ligand gated ion channels
• fast
Neuromodulators
• Neuromodulators are the neurotransmitters, neuropeptides, hormone, temporally
extended effects on the recipient neurons and circuits.
• They are secreted by a small group of neurons diffuse through large areas of the
nervous system affecting multiple neurons.
• Majors are- dopamine, serotonin, acetylcholine, histamine and norepinephrine
• The release of neuromodulators occurs in a diffuse manner k/a volume
transmission
Modes of modulation
Types of neuromodulation
HOW NEUROMODULATION WORKS??
Neuromodulation works by either actively stimulating nerves to produce a natural biological response or by applying
targeted pharmaceutical agents in tiny doses directly to site of action.
NEUROSTIMULATION DEVICES
• involve the application of electrodes to the brain, the spinal
cord or peripheral nerves.
• These precisely placed leads connect via an extension cable to
a pulse generator and power source, which generates the
necessary electrical stimulation.
• A low-voltage electrical current passes from the generator to
the nerve, and can either inhibit pain signals or stimulate
neural impulses where they were previously absent.
Neuromodulatory systems
• Cholinergic
• Dopaminergic
• Serotonergic
• adrenergic
• Co-transmitters, Neuropeptides, Circulating hormones as neuromodulators
Noradrenaline system
• Noradrenaline regulates the activity of both neuronal and non-neuronal cells.
• It participates in the rapid modulation of cortical circuits and cellular energy
metabolism and on a slower time scale in inflammation and neuroplasticity.
• Of the multiple sources of NE in the brain, the locus coeruleus plays a major role
in noradrenergic signaling.
• It plays a critical role in modulating learning and memory via the hippocampus
within the brain.
Dopamine system
• Dopamine is centrally involved in reward, approach, behavior, exploration, and
various aspects of cognition.
• Variations in this neuromodulator function appear to be associated with variations
in personality.
Serotonin system
• It is well-known for its role in the brain where it plays a major part in mood,
anxiety and happiness.
• Over 90% of the body's serotonin is found in the gastrointestinal tract where it has
a role in regulating bowel function and movements.
• It also plays a part in reducing the appetite while consuming a meal(satiety).
Cholinergic system
• Acetylcholine (Ach) has a role in the control of autonomic functions but it is likely
that it also modulate adaptive responses to environmental and metabolic
conditions.
• Cholinergic signaling can influence thermoregulation, sleep patterns, food intake
and endocrine functions including pancreatic insulin and glucagon release.
• ACh signaling in a number of brain areas might also be important for stress
responses as several studies have shown that stress increases its release in a brain.
GABA
• Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal
cord activity.
Neuropeptides
• Opioid peptides - a large family of endogenous neuropeptides that are widely
distributed throughout the central and peripheral nervous system. Opiate drugs
such as heroin and morphine act at the receptors of these neurotransmitters.
1.Endorphins 2.Enkephalins 3.Dynorphins 4.Substance P
Pharmacological applications of Neuromodulation
• Sympathomimetic and sympatholytic drugs: these enhance and block at least some of the effects of
noradrenaline released by the sympathetic nervous system, respectively.
• Dopamine reuptake inhibitors: these prevent dopamine reuptake by blocking the action of the
dopamine transporter. These drugs are frequently used in the treatment of conditions including
depression and narcolepsy.
• Selective serotonin reuptake inhibitors: these temporarily prevent the removal of serotonin from
specific synapses, thereby enhancing the effect of released serotonin. These are used in the treating
depression.
• Cholinesterase inhibitors: these bind to cholinesterase resulting in increased acetylcholine in the
synapses. These are used to treat dementia in patients with Parkinson disease.
Recent Advances
• Neuromodulation also refers to an emerging class of medical therapies that target
the nervous system for restoration of function (such as in cochlear implants), relief
of pain, control of symptoms such as tremor seen in movement disorders like
Parkinson's disease.
• The therapies consist primarily of targeted electrical stimulation, or infusion of
medications into the cerebrospinal fluid using intrathecal drug delivery such as
baclofen for spasticity.
• Electrical stimulation devices include deep brain stimulation systems (DBS),
referred to as "brain pacemakers", spinal cord stimulators (SCS) which are
implanted using minimally invasive procedures or transcutaneous electrical nerve
stimulation devices which are fully external among others.
Methods of neuromodulation
• Invasive electrical neuromodulation methods
• Non-invasive electrical methods
• Non-invasive magnetic methods
• Invasive chemical methods
Invasive electrical neuromodulation methods
• Spinal cord stimulation
• Deep brain stimulation
• Auditory brainstem implant, which provides a sense of sound to a person who
cannot use a cochlear implant due to a damaged or missing cochlea or auditory
nerve
• Functional electrical stimulation (FES) – in paralysis
• Vagus nerve stimulation (VNS) – intractable seizure or depression
• Hypoglossal nerve stimulation used for some patients who have obstructive sleep apnea
• Percutaneous tibial nerve stimulation (PTNS) for the treatment of incontinence.
• Peripheral nerve stimulation (PNS) which refers to simulation of nerves beyond the spine
or brain and may be considered to include occipital or sacral nerve stimulation.
• Occipital nerve stimulation (ONS)
• Sacral nerve stimulation (SNS) / sacral neuromodulation (SNM) - refractory voiding
dysfunction
Spinal Cord Stimulation
• This common form of neuromodulation involves using a device to deliver electrical
current in therapeutic doses to the spinal cord to disrupt pain signals from the spinal cord
to the brain, converting them to a more pleasant tingling sensation. This has been proven
a safe and effective therapeutic approach for managing chronic pain of the arms and legs,
neck and back often after spine surgery or for other neuropathic conditions.
• Stimulation is typically in the 20–200 Hz range though a novel class of stimulation
parameters are now emerging that employ a 10 kHz stimulation train as well as 500 Hz
"burst stimulation".
• The general process for spinal cord stimulation involves a temporary trailing of
appropriate patients with an external pulse generator attached to epidural
electrodes located in the lower thoracic spinal cord.
• The electrodes are placed either via a minimally invasive needle technique (called
percutaneous leads) or an open surgical exposure (surgical "paddle" electrodes).
1. kHz Frequency SCS
2. Burst CS
3. High–Pulse Width SCS Programming
4. Random/Stochastic Stimulation Patterns
• Altering stimulation parameters to subsequently modulate the pathophysiology in chronic pain has become
the focus of therapy development
• Patterns of stimulation can evoke very different responses in multiple regions of the central nervous system,
and thus provide an opportunity to better address the complex neurophysiology in chronic pain.
kHz Frequency SCS
Higher frequencies have also been tested
up to10 kHz
Traditional
40-100 Hz
• Absence of sustained action potential generation in the dorsal columns, despite current amplitudes being at or above threshold.
• This, combined with lower thresholds and pulse amplitudes, effectively
reduces the likelihood of a patient feeling paresthesia
HF-SCS leads are anatomically placed
to span the T9-10 interspace
Lead placement : based
on intraoperative
mapping
burst CS- use specific pulse train
Treatment of diabetic neuropathy, complex regional pain syndrome, and failed back surgery
syndrome
Recover analgesia in patients who have failed or shown accommodation to tonic SCS
Ability to directly and differentially modulate the brain regions involved in the emotional
and affective aspects of the pain experience
Does not seem to alter firing rates of neurons in the dorsal column nuclei so enhanced ability
to modulate pain processing in the dorsal horn without activating the neuronal fibers which
would create the sensation of paresthesia
High–Pulse Width SCS Programming
• To provide an increased ability to modulate neural structures without activating
fibers to the extent that it generates paresthesia
• A higher-charge delivery (or density) over a given period of time.
• Increasing pulse width and frequency increases the charge delivered per second
Random/Stochastic Stimulation Patterns
• For disorders with abnormal neuronal synchrony
• Random stimulation patterns could correct alterations of abnormal synaptic
connectivity and synchrony and also developed to selectively counteract abnormal
neuronal synchrony by eliciting desynchronization
Deep brain stimulation
• DBS therapy has a variety of central nervous system targets depending on the
target pathology. For Parkinson's disease central nervous system targets include
the subthalamic nucleus, globus pallidus interna, and the ventral intermidus
nucleus of the thalamus.
• Dystonias are often treated by implants targeting globus pallidus interna or less
often parts of the ventral thalamic group.
• The anterior thalamus is the target for epilepsy.
• DBS research targets include but are not limited to the following areas: Cg25 for
depression, the anterior limb of the internal capsule for depression as well as
obsessive compulsive disorder (OCD), centromedian/parafasicularis,
centromedian thalamic nuclei and the subthalamic nucleus for OCD, anorexia and
Tourette syndrome, the nucleus accumbens and ventral striatum have also been
assayed for depression and pain.
Headache & VNS
• The vagus nerve is also a target for
the treatment of headache
disorders.
• Patients being treated with a vagus
nerve stimulator for epilepsy had
reduced severity and incidence of
their coexistent migraines
• Non invasive vagus nerve
stimulation (nVNS) at the carotid
artery can be used for prophylactic
and abortive treatment of cluster
and migraine headaches with
reduced cortical spreading
depression and demonstrated
progression in efficacy over time
• The main mechanistic hypothesis is that the
afferent anatomical connection between the
vagus nerve and the trigeminal nucleus
caudalis and the nociceptive inputs from the
dura mater terminating in the nucleus tractus
solitarius are interrupted.
• Neurophysiological evidence showing a
reduction in glutamate levels and neuronal
firing in the spinal trigeminal nucleus
secondary to continuous vagus stimulation
could justify vagal ascending antinociceptive
effects.
SPG STIMULATION
• Treatment for headache
• injections of local anesthetic and has been
subject to neurolysis/radiofrequency ablation to
abort and reduce migraine and cluster
headaches.
• It has shown significant ability to provide pain
relief and reduce the number of headache
days when utilizing neurostimulationof the
SPG for upto 2 years
Given the role that the SPG plays in
autonomic regulation within the
head
• parasympathetic outflow to the
periorbital, nasal, meningeal, and
cerebral blood vessels
All-in-one small stimulator designed specifically
for sphenopalatine ganglion stimulation
Trigeminal System Stimulation
• neuromodulation for the
treatment of trigeminal
neuralgia and intractable facial
pain might provide good relief
• Neuroablative procedures of
the trigeminal nucleus caudalis
and spinal trigeminal tract have
resulted in pain relief
• The average coverage in the pain zone was 72%,
and average 57.1% pain reduction.
o The long-term treatment failure rate was 25%.
Upper cervical Spinal cord
stimulation
Non invasive
• To stimulate supraorbital nerve, branch of V1
• benefit in acute migraine
Occipital Nerve Stimulation
(ONS)
• Greater & lesser occipital nerves
send afferent projections through
C2-3 dorsal roots
• Stimulation of this afferent
pathway may downstream
trigeminal dysfunction in head and
facial pain.
1. headaches, including
cervicogenic, migraine, cluster,
and occipital neuralgia
Clinical Application of ONS
Non-invasive electrical methods
• These methods use external electrodes to apply a current to the body in order to
change the functioning of the nervous system.
• Methods include:
• Transcranial direct current stimulation (tDCS)- use in brain injury or depression
• Transcutaneous electrical nerve stimulation(TENS) and a prescription variant
of TENS transcutaneous afferent patterned stimulation (TAPS)
• Electroconvulsive therapy (ECT)
Non-invasive magnetic methods
• Magnetic methods of neuromodulation are normally non-invasive.
• No surgery is required to allow a magnetic field to enter the body
because the magnetic permeability of tissue is similar to that of air. In
other words magnetic fields penetrate the body very easily.
• The two main techniques are highly related in that both use changes in magnetic
field strength to induce electric fields and ionic currents in the body. There are
however differences in approach and hardware.
• Repetitive transcranial magnetic stimulation (rTMS)- the stimulation has a high
amplitude (0.5–3 tesla), a low complexity and anatomical specificity is reached
through a highly focal magnetic field
• Transcranial pulsed electromagnetic fields (tPEMF)- the stimulation
has a low amplitude (0.01–500 millitesla) a high complexity and
anatomical specificity is reached through the specific frequency
content of the signal.
Invasive chemical methods
• Chemical neuromodulation is always invasive because a drug is delivered in a
highly specific location of the body. The non-invasive variant is
traditional pharmacotherapy e.g. swallowing a tablet.
• Intrathecal drug delivery systems (ITDS) which may deliver micro-doses of
painkiller (exm-ziconotide) or anti-spasm medicine (such as baclofen) directly to
the site of action.
Thank you

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Neuromodulation

  • 1. NEUROMODULATION Dr VIKAS KUMAR DWIVEDI Neurosurgery department SGPGI
  • 2. WHAT is Neuromodulation??? • Neuromodulation is the targeted release of a substance from a neuron that alters the efficacy of synaptic transmission or the cellular properties of neuron • It is the physiological process by which a given neuron uses one or more neurotransmitters to regulate diverse populations
  • 3. There is targeted delivery of a stimulus, such as electrical stimulation or chemical agents to specific neurological sites in the body". It is carried out to normalize – or modulate – nervous tissue function.
  • 4. NEUROMODULATION Vs SYNAPTIC TRANSMISSION NEUROMODULATION • It occurs when a substance released from one neuron alters the cellular or synaptic properties of another neuron • G protein coupled receptors • slow SYNAPTIC TRANSMISSION • One presynaptic neuron directly influnces a single postsynaptics partner • Ligand gated ion channels • fast
  • 5. Neuromodulators • Neuromodulators are the neurotransmitters, neuropeptides, hormone, temporally extended effects on the recipient neurons and circuits. • They are secreted by a small group of neurons diffuse through large areas of the nervous system affecting multiple neurons. • Majors are- dopamine, serotonin, acetylcholine, histamine and norepinephrine • The release of neuromodulators occurs in a diffuse manner k/a volume transmission
  • 8. HOW NEUROMODULATION WORKS?? Neuromodulation works by either actively stimulating nerves to produce a natural biological response or by applying targeted pharmaceutical agents in tiny doses directly to site of action. NEUROSTIMULATION DEVICES • involve the application of electrodes to the brain, the spinal cord or peripheral nerves. • These precisely placed leads connect via an extension cable to a pulse generator and power source, which generates the necessary electrical stimulation. • A low-voltage electrical current passes from the generator to the nerve, and can either inhibit pain signals or stimulate neural impulses where they were previously absent.
  • 9. Neuromodulatory systems • Cholinergic • Dopaminergic • Serotonergic • adrenergic • Co-transmitters, Neuropeptides, Circulating hormones as neuromodulators
  • 10.
  • 11. Noradrenaline system • Noradrenaline regulates the activity of both neuronal and non-neuronal cells. • It participates in the rapid modulation of cortical circuits and cellular energy metabolism and on a slower time scale in inflammation and neuroplasticity. • Of the multiple sources of NE in the brain, the locus coeruleus plays a major role in noradrenergic signaling. • It plays a critical role in modulating learning and memory via the hippocampus within the brain.
  • 12. Dopamine system • Dopamine is centrally involved in reward, approach, behavior, exploration, and various aspects of cognition. • Variations in this neuromodulator function appear to be associated with variations in personality.
  • 13. Serotonin system • It is well-known for its role in the brain where it plays a major part in mood, anxiety and happiness. • Over 90% of the body's serotonin is found in the gastrointestinal tract where it has a role in regulating bowel function and movements. • It also plays a part in reducing the appetite while consuming a meal(satiety).
  • 14. Cholinergic system • Acetylcholine (Ach) has a role in the control of autonomic functions but it is likely that it also modulate adaptive responses to environmental and metabolic conditions. • Cholinergic signaling can influence thermoregulation, sleep patterns, food intake and endocrine functions including pancreatic insulin and glucagon release. • ACh signaling in a number of brain areas might also be important for stress responses as several studies have shown that stress increases its release in a brain.
  • 15. GABA • Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity. Neuropeptides • Opioid peptides - a large family of endogenous neuropeptides that are widely distributed throughout the central and peripheral nervous system. Opiate drugs such as heroin and morphine act at the receptors of these neurotransmitters. 1.Endorphins 2.Enkephalins 3.Dynorphins 4.Substance P
  • 16. Pharmacological applications of Neuromodulation • Sympathomimetic and sympatholytic drugs: these enhance and block at least some of the effects of noradrenaline released by the sympathetic nervous system, respectively. • Dopamine reuptake inhibitors: these prevent dopamine reuptake by blocking the action of the dopamine transporter. These drugs are frequently used in the treatment of conditions including depression and narcolepsy. • Selective serotonin reuptake inhibitors: these temporarily prevent the removal of serotonin from specific synapses, thereby enhancing the effect of released serotonin. These are used in the treating depression. • Cholinesterase inhibitors: these bind to cholinesterase resulting in increased acetylcholine in the synapses. These are used to treat dementia in patients with Parkinson disease.
  • 17. Recent Advances • Neuromodulation also refers to an emerging class of medical therapies that target the nervous system for restoration of function (such as in cochlear implants), relief of pain, control of symptoms such as tremor seen in movement disorders like Parkinson's disease. • The therapies consist primarily of targeted electrical stimulation, or infusion of medications into the cerebrospinal fluid using intrathecal drug delivery such as baclofen for spasticity.
  • 18. • Electrical stimulation devices include deep brain stimulation systems (DBS), referred to as "brain pacemakers", spinal cord stimulators (SCS) which are implanted using minimally invasive procedures or transcutaneous electrical nerve stimulation devices which are fully external among others.
  • 19. Methods of neuromodulation • Invasive electrical neuromodulation methods • Non-invasive electrical methods • Non-invasive magnetic methods • Invasive chemical methods
  • 20. Invasive electrical neuromodulation methods • Spinal cord stimulation • Deep brain stimulation • Auditory brainstem implant, which provides a sense of sound to a person who cannot use a cochlear implant due to a damaged or missing cochlea or auditory nerve • Functional electrical stimulation (FES) – in paralysis • Vagus nerve stimulation (VNS) – intractable seizure or depression
  • 21. • Hypoglossal nerve stimulation used for some patients who have obstructive sleep apnea • Percutaneous tibial nerve stimulation (PTNS) for the treatment of incontinence. • Peripheral nerve stimulation (PNS) which refers to simulation of nerves beyond the spine or brain and may be considered to include occipital or sacral nerve stimulation. • Occipital nerve stimulation (ONS) • Sacral nerve stimulation (SNS) / sacral neuromodulation (SNM) - refractory voiding dysfunction
  • 22.
  • 23. Spinal Cord Stimulation • This common form of neuromodulation involves using a device to deliver electrical current in therapeutic doses to the spinal cord to disrupt pain signals from the spinal cord to the brain, converting them to a more pleasant tingling sensation. This has been proven a safe and effective therapeutic approach for managing chronic pain of the arms and legs, neck and back often after spine surgery or for other neuropathic conditions. • Stimulation is typically in the 20–200 Hz range though a novel class of stimulation parameters are now emerging that employ a 10 kHz stimulation train as well as 500 Hz "burst stimulation".
  • 24. • The general process for spinal cord stimulation involves a temporary trailing of appropriate patients with an external pulse generator attached to epidural electrodes located in the lower thoracic spinal cord. • The electrodes are placed either via a minimally invasive needle technique (called percutaneous leads) or an open surgical exposure (surgical "paddle" electrodes).
  • 25. 1. kHz Frequency SCS 2. Burst CS 3. High–Pulse Width SCS Programming 4. Random/Stochastic Stimulation Patterns • Altering stimulation parameters to subsequently modulate the pathophysiology in chronic pain has become the focus of therapy development • Patterns of stimulation can evoke very different responses in multiple regions of the central nervous system, and thus provide an opportunity to better address the complex neurophysiology in chronic pain.
  • 26. kHz Frequency SCS Higher frequencies have also been tested up to10 kHz Traditional 40-100 Hz • Absence of sustained action potential generation in the dorsal columns, despite current amplitudes being at or above threshold. • This, combined with lower thresholds and pulse amplitudes, effectively reduces the likelihood of a patient feeling paresthesia HF-SCS leads are anatomically placed to span the T9-10 interspace Lead placement : based on intraoperative mapping
  • 27. burst CS- use specific pulse train Treatment of diabetic neuropathy, complex regional pain syndrome, and failed back surgery syndrome Recover analgesia in patients who have failed or shown accommodation to tonic SCS Ability to directly and differentially modulate the brain regions involved in the emotional and affective aspects of the pain experience Does not seem to alter firing rates of neurons in the dorsal column nuclei so enhanced ability to modulate pain processing in the dorsal horn without activating the neuronal fibers which would create the sensation of paresthesia
  • 28. High–Pulse Width SCS Programming • To provide an increased ability to modulate neural structures without activating fibers to the extent that it generates paresthesia • A higher-charge delivery (or density) over a given period of time. • Increasing pulse width and frequency increases the charge delivered per second
  • 29. Random/Stochastic Stimulation Patterns • For disorders with abnormal neuronal synchrony • Random stimulation patterns could correct alterations of abnormal synaptic connectivity and synchrony and also developed to selectively counteract abnormal neuronal synchrony by eliciting desynchronization
  • 30. Deep brain stimulation • DBS therapy has a variety of central nervous system targets depending on the target pathology. For Parkinson's disease central nervous system targets include the subthalamic nucleus, globus pallidus interna, and the ventral intermidus nucleus of the thalamus. • Dystonias are often treated by implants targeting globus pallidus interna or less often parts of the ventral thalamic group. • The anterior thalamus is the target for epilepsy.
  • 31. • DBS research targets include but are not limited to the following areas: Cg25 for depression, the anterior limb of the internal capsule for depression as well as obsessive compulsive disorder (OCD), centromedian/parafasicularis, centromedian thalamic nuclei and the subthalamic nucleus for OCD, anorexia and Tourette syndrome, the nucleus accumbens and ventral striatum have also been assayed for depression and pain.
  • 32. Headache & VNS • The vagus nerve is also a target for the treatment of headache disorders. • Patients being treated with a vagus nerve stimulator for epilepsy had reduced severity and incidence of their coexistent migraines • Non invasive vagus nerve stimulation (nVNS) at the carotid artery can be used for prophylactic and abortive treatment of cluster and migraine headaches with reduced cortical spreading depression and demonstrated progression in efficacy over time • The main mechanistic hypothesis is that the afferent anatomical connection between the vagus nerve and the trigeminal nucleus caudalis and the nociceptive inputs from the dura mater terminating in the nucleus tractus solitarius are interrupted. • Neurophysiological evidence showing a reduction in glutamate levels and neuronal firing in the spinal trigeminal nucleus secondary to continuous vagus stimulation could justify vagal ascending antinociceptive effects.
  • 33. SPG STIMULATION • Treatment for headache • injections of local anesthetic and has been subject to neurolysis/radiofrequency ablation to abort and reduce migraine and cluster headaches. • It has shown significant ability to provide pain relief and reduce the number of headache days when utilizing neurostimulationof the SPG for upto 2 years Given the role that the SPG plays in autonomic regulation within the head • parasympathetic outflow to the periorbital, nasal, meningeal, and cerebral blood vessels All-in-one small stimulator designed specifically for sphenopalatine ganglion stimulation
  • 34. Trigeminal System Stimulation • neuromodulation for the treatment of trigeminal neuralgia and intractable facial pain might provide good relief • Neuroablative procedures of the trigeminal nucleus caudalis and spinal trigeminal tract have resulted in pain relief • The average coverage in the pain zone was 72%, and average 57.1% pain reduction. o The long-term treatment failure rate was 25%. Upper cervical Spinal cord stimulation Non invasive • To stimulate supraorbital nerve, branch of V1 • benefit in acute migraine
  • 35. Occipital Nerve Stimulation (ONS) • Greater & lesser occipital nerves send afferent projections through C2-3 dorsal roots • Stimulation of this afferent pathway may downstream trigeminal dysfunction in head and facial pain. 1. headaches, including cervicogenic, migraine, cluster, and occipital neuralgia Clinical Application of ONS
  • 36. Non-invasive electrical methods • These methods use external electrodes to apply a current to the body in order to change the functioning of the nervous system. • Methods include: • Transcranial direct current stimulation (tDCS)- use in brain injury or depression • Transcutaneous electrical nerve stimulation(TENS) and a prescription variant of TENS transcutaneous afferent patterned stimulation (TAPS) • Electroconvulsive therapy (ECT)
  • 37. Non-invasive magnetic methods • Magnetic methods of neuromodulation are normally non-invasive. • No surgery is required to allow a magnetic field to enter the body because the magnetic permeability of tissue is similar to that of air. In other words magnetic fields penetrate the body very easily.
  • 38. • The two main techniques are highly related in that both use changes in magnetic field strength to induce electric fields and ionic currents in the body. There are however differences in approach and hardware. • Repetitive transcranial magnetic stimulation (rTMS)- the stimulation has a high amplitude (0.5–3 tesla), a low complexity and anatomical specificity is reached through a highly focal magnetic field
  • 39. • Transcranial pulsed electromagnetic fields (tPEMF)- the stimulation has a low amplitude (0.01–500 millitesla) a high complexity and anatomical specificity is reached through the specific frequency content of the signal.
  • 40. Invasive chemical methods • Chemical neuromodulation is always invasive because a drug is delivered in a highly specific location of the body. The non-invasive variant is traditional pharmacotherapy e.g. swallowing a tablet. • Intrathecal drug delivery systems (ITDS) which may deliver micro-doses of painkiller (exm-ziconotide) or anti-spasm medicine (such as baclofen) directly to the site of action.