PAIN 신형철 교수 본3본3 is critical for our survival. PAIN: -definition of pain: an unpleasant sensory or emotional experience -perception of pain: a product.

PAIN

신형철 교수

본 3

is critical for our survival

PAIN:-definition of pain: an unpleasant sensory or emotional experience

-perception of pain: a product of brain’s abstraction and elaboration of sensory input.

perception of pain varies with individuals and circumstances (soldier injured)

-activation of nociceptors does not necessarily lead to experience of pain (asymbolia for pain; patient under morphine)

-pain can be perceived without activation of nociceptors (phantom limb pain, thalamic pain syndrome)

-important for survival, protect from damage: congenital and acquired insensitivity (diabetic neuropathy, neurosyphilis) to pain can lead to permanent damage

-pain reflexes can be stopped if not appropriate (step on nail near precipice, burn hands while holding a baby. Pain can be suppressed if not needed for survival (soldier…).

In general 2 clinical states of pain:

Physiological (nociceptive) pain direct stimulation of nociceptors.

Neuropathic (intractable) pain result from injury to the peripheral or central nervous system that causes permanent changes in circuit sensitivity and CNS connections.

Relationship between injury and pain do not coincide.

A. Injury but No Pain

First, because of nerve damage affecting the part of the body that is injured.

Second, there are some tissues in our bodies that are relatively insensitive to injury. most of the brain tissue itself is insensitive to pain.

Third, there is evidence that people with intact nervous systems can have injuries but no pain. not clearly understood

Fourth, persons to have injuries and not experience pain because their minds are involved in something else that is considered more important at the moment.

B. Pain but No Injury

*phantom limb pain* thalamic pain syndrome following a stroke.* imagined pain is every bit as real as pain experienced by

persons with verified physical injuries.http://rds.yahoo.com/_ylt=A9G_f4HzJOlFADgBl2UCP88F;_ylu=X3oDMTBkM3VyNWF1BHBvcwMxNQRzZWMDc3I-/SIG=189vm79mk/EXP=1172993651/**http://video.yahoo.com/video/play?ei=UTF-8&p=chronic+pain&b=14&oid=01c541dcd789dbe4&rurl=g6publish.videodome.com&vdone=http%3A%2F%2Fvideo.yahoo.com%2Fvideo%2Fsearch%3Fei%3DUTF-8%26p%3Dchronic%2Bpain%26b%3D11

This resiliency of pain processing mechanisms is clearly in evidence in many cases of chronic pain - pain which persists long after healing has occurred.

Many forms of chronic pain, particularly those arising from damage to nerves, fail to respond to conventional treatments and cause an incalculable degree of both emotional and economic hardship.

Individuals who are born without this capacity frequently die at relatively young ages from injuries that they never felt.

Pain Information processing is distributed across multiple brain regions and transmitted via parallel pathways. Thus, if any one pathway or region becomes damaged, other regions and other pathways are still available to contribute to this experience.

The market for all pain therapies was US$17 billion in 2000, and is expected to grow to $25 billion, $33 billion and $41 billion by 2001, 2005 and 2010 of which an increasing proportion will be for chronic pain conditions.

Events that can cause pain

* excessive stimulation of a sensory organ * external pressure on a nerve - pinched nerve * nerve damage - generally not repairable * exceeding thresholds of cold, heat, pressure * swelling of an internal organ * extended contraction of a muscle * muscle spasms * low blood flow to an organ

Components of Pain

1. Sensory discriminative: when started and ended, where, how long 2. Affective (emotional): unpleasant 3. Autonomic: blood pressure, heart rate, respiration, visceral pain 4. Motor: escape of protection reflex 5. Cognitive: evaluation of pain, past experience

Many Systems are simultaneously or separately involved Variability of pain sensation depends on situation, education, society etc.

PAIN LOCATION

A. Somatic 1) Superficial(initial & delayed)

2) Deepe.g., chronic, acute joint pain

B. Visceral

PAIN Duration

1. Acute Pain: e.g., burning, where, how long: Signal & warning function

2. Chronic Pain: e.g., back pain, tumor, migrane headache : No Physiological Function: Real damage---not equal to the degree of pain sensation: Location ...... separate syndrome : psychogenic pain

Chronic Pain Syndrome Refers to the collection of additional problems which frequently accompany chronic pain conditions. They may include any combination of the following:

•Interference with work and leisure-time activities * Decreased income, increased financial pressures * Activity intolerance

•* Reduced social activities, social withdrawal * Feelings of depression & discouragement, anger & irritability, tension * Decreased interest in previously enjoyed activities combined with increased preoccupation with pain

•* Interference with concentration and memory * Decreased self-confidence and self-esteem * Negative attitudes regarding self, others, and life in general

•* Misuse of pain medications or alcohol * Development of secondary physical problems and complaints * Sleep difficulties

•* Decreased sexual interest and/or problems with sexual performance

* Conflicts with medical providers and disability compensation systems Not everyone with chronic pain possesses all features of the chronic pain syndrome.

Nociceptors

Mechanical nociceptors activated by strong stimuli such as pinch, and sharp objects that penetrate, squeeze, pinch the skin. sharp or pricking pain, via A-delta fibers.

Thermal nociceptors activated by noxious heat (temp. above 45°C), noxious cold (temp. below 5°C), and strong mechanical stimuli. via A-delta fibers.

Polymodal nociceptors activated by noxious mechanical stimuli, noxious heat, noxious cold, irritant chemicals. slow dull burning pain or aching pain, via non-myelinated C fibers. Persists long after the stimulus is removed.

A-deltaMylenated2-5 um, 6-30 m/secA-Fiber Mechano-Heat nociceptors "First Pain": Early, Brief, Sharp, and Pricking Excitatory amino acids (glutamate, aspartate, or ATP) Light Pressure, Heavy Pressure, Heat (45+ deg. Cent.), Chemicals, Cooling

C-Fiber Unmylenated0.3-3.0 um, 1-2.5 m/secC-PolyModal Nociceptor "Second Pain": Slow, Dull, and Burning Glutamate, Substance P (however, there are C-nociceptors without Substance P), Neurokinins A&B, Cholycstokinin, CGRP, Vasointestinal peptide Light Pressure, Heavy Pressure, Heat (45+ deg. Cent.), Chemicals, Warmth

Nociceptors

1. The nociceptors (pain sensitive) sensory endings associated with C fibers are polymodal. They respond to a number of stimuli including: heat, mechanical stimuli and chemicals. C fibers are non-myelinated and conduct slowly at 0.5 - 2 m/sec.

2. The nociceptor sensory endings associated with A-delta fibers respond to thermal or mechanical stimuli. A-delta fibers are myelinated and conduct at 5-30 m/sec.

3. The end of nociceptor neurons are not specialized as with other sensory neurons but are bare (free) nerve endings.

Pain Sensory Receptors

1. Heat sensitive receptorsAbove a threshold of 43oC these heat activated channels will open, allow cations (Na+ in particular) to flow into the cell thus causing a depolarization. The greater the stimulus temperature above threshold the greater the frequency of action potential firing. (These neurons are distinct from the heat sensitive sensory neurons which will respond to increasing temperatures that are non-painful. The two types of sensory neurons are active in different temperature ranges).

2. pH-gated channelsAcid sensing channel, responds to pHs below 6.5 (stimulated by tissue damage or anoxic/overactive cells). Some of these receptors have recently been shown to be the same as the capsaicin receptor (Tominaga et al., 1999)

3. ATP gated channelsATP is released from damaged cells. ATP-gated ion channels found in nociceptors.

4. BradykininDamaged cells release proteolytic enzymes which result in the break down of a preprotein into a nine amino acid peptide called bradykinin. Bradykinin binds to its B2 receptor which belongs to the metabotropic class of receptors i.e. 7 transmembrane receptor linked to a G protein. Activation of the B2 receptor triggers a second messanger that activates a transient inward current (Na+ channel) to depolarize the sensory neuron.

5. K+K+ ions will be released after damage to surrounding cells. This will increase the extracellular concentration of K+ around the pain sensory neuron ending and result in a depolarzation of the neuron.

Mechanisms associated with peripheral sensitization to

pain

Agents that Activate or Sensitize Nociceptors:Cell injury arachidonic acid prostaglandins vasc. permeability (cyclo-oxygenase) sensitizes nociceptor

Cell injury arachidonic acid leukotrienes vasc. permeability (lipoxygenase) sensitizes nociceptor

Cell injury tissue acidity kallikrein bradykinin vasc. permeability

activates nociceptors

synthesis & release of prostaglandins

Substance P (released by free nerve endings) sensitize nociceptors

vasc. perm., plasma extravasation

(neurogenic inflammation)

releases histamine (from mast cells)

Calcitonin gene related peptide (free nerve endings) dilation of peripheral capillaries

Serotonin (released from platelets & damaged endothelial cells) activates nociceptors

Cell injury potassium activates nociceptors

Peripheral sensitization to pain:

Some definitions:

Hyperalgesia increased sensitivity to an already painful stimulus

Allodynia normally non painful stimuli are felt as painful (i.e .light touch of a sun-burned skin)

Allodynia

Root of the Term : "allo" meaning "other" + "odyne" meaning pain

Definition: Pain due to a stimulus that does not normally provoke pain.

Characteristics: non-noxious tactile, thermal stimuli--->painful shift (change) of sensory modality Difference from Hyperalgesia?

Analgesics and Anesthetics

Analgesia - reduction of sensibility to pain, production of loss of pain sensation without loss of consciousness or other vital functions in response to stimuli that would normally be painful.

Anesthesia - absence of all sensory modality and loss of consciousness without loss of vital functions

CGRP

CGRP

Peripheral sensitization to pain:

Serotonin, bradykinin, histamine, prostaglandins, substance P (sP) , and various ions (ie, H+ or K+)--the biochemical mediators released as a result of tissue injury--have been implicated in nociceptive activation and sensitization (hyperalgesia).

Hyperalgesia results in enhancement of spontaneous pain via1) a reduction in pain threshold 2) and a lengthening in duration of nociceptor response to stimuli. PGE1, PGE2, and PGF2a, are the most potent prostaglandins to produce these sensitization effects.

Substance P, synthesized by cells of the spinal ganglia, has been identified at the peripheral terminal of unmyelinated primary afferent fibers. suggested that this putative neurotransmitter may play a role in the propagation of visceral nociceptive pain from the gastrointestinal (GI) tract, ureters, and urinary bladder. In addition, to SP, other potential nociceptive transmitters include glutamate, aspartate, somatostatin, cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP).

To summarize peripheral sensitization to pain

-Sensitization results from the release of various chemicals by the damaged cells and tissues (bradykinin, prostaglandins, leukotrienes…). These chemicals (algogenic substances) alter the type and number of membrane receptors on free nerve endings, lowering the threshold for nociceptive stimuli.

-The depolarized nociceptive sensory endings release substance P and CGRP along their branches (axon reflex), thus contributing to the spread of edema by producing vasodilation, increase in vascular permeability and plasma transvasation, and the spread of hyperalgesia by leading to the release of histamine from mast cells.

-Aspirin and NSAID (nonsteroidal anti-inflammatory drug) block the formation of prostaglandins by inhibiting the enzyme cyclooxygenase.

-Local anesthetic preferentially blocks C-fiber conduction, cold decreases firing of C-fibers, ischemia blocks first the large myelinated fibers.

Pathophysiology of Transduction

Injury to somatic (skin, muscle, or bone) or to visceral tissues is known as nociceptive pain.

Pressure from a mass that encircles and constricts neural tissue (e.g., nerve plexus, nerve root, spinal cord) and that is sufficient to injure the tissue, produces pain known as neuropathic pain.

Burns are obvious examples of tissue damage from thermal stimuli. Superficial burns injure somatic tissue and result in nociceptive pain. Massive burns, however, are likely to injure peripheral nerve fibers as well as somatic tissues. Therefore, extensive burns may result in both neuropathic and nociceptive types of pain.

Neuropathic (intractable) pain:

Pain following peripheral nerve injury. Greater loss of small fibers than large diameter fibers. Axons of surviving A-beta fibers sprout new branches and make connection to neurons vacated by the lost C fibers . Non-painful stimuli become painful. Change from innocuous to noxious sensation is called allodynia.

Thalamic pain syndrome: usually following stroke in the ventral basal thalamus. Rearrangement of local circuit leads to excruciating pain.

Phantom limb pain:

A-beta

C fibersPain

Signalingneurons

N

Afferents to Spinal Dorsal Horn layer I (marginal zone): A-delta, high density of projection neurons layer II (substantia gelatinosa): C-fibers, output layer III layer III: from layer II (C input) layer IV: A-alpha & A-beta, from layer V (A-delta)

layer V: A-delta, output to layer IV

Thus: lamina V cells details about the stimulus, and lamina I cells whether it is painful or not

-A-delta and C fibers release glutamate and peptides on dorsal horn neurons.

-Substance P (SP) is co-released with glutamate and enhances and prolongs the actions of glutamate.

-Glutamate action is confined to nearby neurons but SP can diffuse and affect other populations of neurons because there is no specific reuptake.

Pain input to the spinal cord:

-Projecting neurons in lamina I receive A-delta and C fibers info.

-Neurons in lamina II receive input from C fibers and relay it to other laminae.

-Projecting neurons in lamina V (wide-dynamic range neurons) receive A-delta, C and A-beta (low threshold mechanoceptors) fibers information.How is pain info sent to the brain: hypotheses pain is signaled by lamina I and V neurons acting together. If lamina I cells are not active, the info about type and location of a stimulus provided by lamina V neurons is interpreted as innocuous. If lamina I cells are active then it is pain.

types of neurons: Projection N.: relay incoming sensory information to higher ctrs. Local excitatory N.: relay sensory input to projection neurons. Inhibitory N.: regulate the flow of nociceptive information

Two Major Nocicpetive Cell Types:

Noceceptive specific N. (NS, HT): layer I excited soley by nociceptors Wide Dynamic Range N. (WDR): layer I, V & VI excited by nociceptors & by low-threshold mechanoreceptors

Neurotransmitters: Glutamate, Substance P, Enkephalin 등등 :small electron-translucent synaptic vesicles: excitatory amino acids A-delta fiber 에 다 , evokes fast synaptic potentials

:large dense-core vesicles: neuropeptides C-fiber 에 다 , elicit slow excitatory PSP

Ascending Pathways:->localization, intensity, type of pain stimulus

->arousal, emotion; involves limbic system,amygdala, insula, cingulate cortex, hypothalamus.Mediate descending control of pain (feedback loop)

Centrally mediated hyperalgesia:Under conditions of persistent injury, C fibers fire repetitively and the response of dorsal horn neurons increase progressively (“wind-up” phenomenon). This is due to activation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and diffusion of substance P that sensitizes adjacent neurons. Blocking NMDA receptors can block the wind-up.

Noxious stimulation can produce these long-term changes in dorsal neurons excitability (central sensitization) which constitute a memory of the C fiber input. Can lead to spontaneous pain and decreases in the threshold for the production of pain.

Carpal tunnel syndrome: median nerve frequently injured at the flexor retinaculum. Pain ends up affecting the entire arm. (rat model partial ligature of sciatic nerve or nerve wrapped with irritant solution)

Mechanisms of early-onset central sensitization:

Winduphomosynaptic activity-dependent plasticity characterized by a progressive increase in firing from dorsal horn neurons during a train of repeated low-frequency C-fiber or nociceptor stimulation.

During stimulation, glutamate + substance P + CGRP elicit slow synaptic potentials lasting several-hundred milliseconds. Windup results from the summation of these slow synaptic potentials. This produces a cumulative depolarization that leads to removal of the voltage-dependent Mg2+ channel blockade in NMDA receptors and entry of Ca2+. Increasing glutamate action progressively increases the firing-response to each individual stimulus (behavioral correlate: repeated mechanical or noxious heat are perceived as more and more painful even if the stimulus intensity does not change.

Both the thalamus (lower activation focus) and the primary somatosensory cortex (upper activation focus) are activated by acute pain produced by injection of capsaicin (chile pepper extract) into the skin.

Regional activations are determined by statistical analysis of positron emission tomography (PET) scans from 14 subjects.

Itch: Anatomy & PhysiologyPeripheral Stimuli

Histamine Onset: Delay of 30 to 60 seconds Duration: 10 minutes

Itch axons are mechanically insensitive Mustard oil: Stimulates distinct axons conveying dysesthesias associated with itch

Primary itch afferents C-fibers Physiology

Transcutaneous electrical threshhold: High Conduction velocity: Low Mechanical stimuli: Unresponsive Histamine sensitive

Secondary itch afferents Location of cell bodies: Lamina I of spinal dorsal grey Projection pathway

Spinothalamic tract Conduction velocity of axons: Slow

Termination: Thalamic nuclei Ventral posterior inferior (VPI) Periphery of Ventral posterior lateral (vVPL)

Inhibited by painful stimuli

Neural Mechanisms of Itch Sensation

What are the signs and symptoms of the condition?

What are the causes and risks of the condition?

What can be done to prevent the condition?

How is the condition diagnosed?

What are the treatments for the condition?

Causes of Visceral pain

1. Extreme expansion of gut, bladder2. ischemia-->Strong contraction or severe stretching of muscular wall 3. Mechanical or chemical (acid, base) stimulation of mucosal layer

Unmyelinated Vagus nerve (mechano, chemoreceptor: gastric motility, secretion)

Referred Pain:

stomach problems may refer to the spine between the shoulder blades. a problem in the throat may be referred to the ear.

intestinal dysfunction may be felt in the middle or low back.

Visceral pain and its Management

New pathway for visceral pain:

selective lesion of fibers in the ventral part of the fasciculus gracilis reduces dramatically the perception of pain from the viscera.

General problems with surgery:

Rhizotomy (cutting dorsal root)

Anterolateral cordotomy (cutting ALS)

In both cases, pain come back, excruciating.

Thalamus: lesion VPL, VPM thalamic syndrome. Intralaminar nuclei (arousal + limbic)

Cortex: S1 cortex localization, quality and intensity of pain stimuli. Lesion of cingulate gyrus and insular cortex asymbolia for pain

Gate Control Hypothesis

Wall & Melzack 1965Hypothesized interneurons activated by A-beta fibers act as a gate, controlling primarily the transmission of pain stimuli conveyed by C fibers to higher centers.

i.e. rubbing the skin near the site of injury to feel better.

i.e. Transcutaneous electrical nerve stimulation (TENS).

i.e. dorsal column stim.

i.e. Acupuncture

Gate Control Theory of Pain:

Therapeutic implications of the gate control theory

1. stimulation of tactile fibers of the skin inhibits the transmission of pain signals from the same area of the body. e.g., rubbing, stroking, massage, vibration, application of liniments and other ointments.

2. electrical stimulation of the skin's sensory nerve fibers (transcutaneous electrical nerve stimulators [TENS]) inhibits pain. 3. morphine and other opioid drugs inhibit or block SG activity and, thus, pain.

4. normal and excessive environmental stimuli can close the pain gate.

5. the pain gate can be closed by inhibitory signals from the cerebral cortex and thalamus. e.g., decreasing anxiety, fear, teaching the client

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http://www.metacafe.com/watch/227740/no_more_pain/

HYPNOSIS MIGHT ALLEVIATE pain by decreasing the activity of brain areas involved in the experience of suffering.

Positron emission tomography (PET) scans of horizontal (top) and vertical (bottom) brain sections were taken while the hands of hypnotized volunteers were sunk into painfully hot water.

The activity of the somatosensory cortex, which processes physical stimuli, did not differ whether a subject was given the hypnotic suggestion that the sensation would be painfully hot (left) or that it would be minimally unpleasant (right).

In contrast, a part of the brain known to be involved in the suffering aspect of pain, the anterior cingulate cortex, was much less active when subjects were told that the pain would be minimally unpleasant (bottom).

1. proopiomelanocortin (POMC) gene2. proenkephalin gene3. prodynorphin gene

three peptides are distributed differently in the CNS

two inhibitory mechanisms1. postsynaptic inhibition produced partly by increasing K+ conductance2. by presynaptic inhibition

Descending pathways regulating the transmission of pain information:

intensity of pain varies among individuals and depends on circumstances (i.e. soldier wounded, athlete injured, during stress).

Stimulation of PAG causes analgesia so profound that surgery can be performed.

PAG stimulation can ameliorate intractable pain. PAG receives pain information via the spinomesencephalic tract and inputs from cortex and hypothalamus related to behavioral states and to whether to activate the pain control system. PAG acts on raphe & locus ceruleus to inhibit dorsal horn neurons via interneurons and morphine receptors.

Application: Intrathecal morphine pumps

Three classes of opioid receptors

mu, d-delta and kappa genes cloned and found to be members of the G protein receptors. •Types

om Receptor •Agonists: Morphine; [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) •Antagonist: H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) •System stimulation: Reduces acute pain & hyperalgesia in most models

od Receptor •Agonist: 4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) •Antagonist: Naltrindole •System stimulation: Reduces acute pain & hyperalgesia in inflammatory pain models •May have fewer side effects (Constipation, respiratory depression, physical dependence) than m-agonists

ok Receptor •Agonist: (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cylcohexyl]-benzeneacetamide hydrochloride (U50,488) •System stimulation: No effect on chronic muscle pain

•Locations: PAGM, Ventral medulla, Dorsal horn

Factors that influence the production of enkephalins, endorphins, dynomorphins

1. prolonged strenuous activity 2. TENS 3. acupuncture 4. placebo effect

Following are some situations and conditions which are thought to stimulate endorphin production. 1) Emergency situations requiring the person to perform physical actions despite pain and injury. 2) Intense physical activity. Moderate physical activity over an extended period of time can also increase the supply of endorphin. 3) Positive beliefs and expectations (e.g., the "placebo effect"). 4) Positive emotional states such as happiness, joy, laughter, and love.

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Analgesics:

1) May act at the site of injury and decrease the pain associated with an inflammatory reaction (e.g. non-steroidal anti-inflammatory drugs (NSAID) such as: aspirin, ibuprofen, diclofenac). Believed to act through inhibition of cyclo-oxygenase (COX). COX-2 is induced at sites of inflammation. Inhibition of COX-1 causes the unwanted effects of NSAID, i.e. gastrointestinal bleeding and nephrotoxicity. Selective COX-2 inhibitor are now used.

2) May alter nerve conduction (e.g. local anesthetics): block action potentials by blocking Na channels. Used for surface anesthesia, infiltration, spinal or epidural anesthesia. Used in combination to steroid to reduce local swelling (injection near nerve root). Local anesthetic preferentially blocks C fiber conduction, cold decreases firing of C fibers, ischemia blocks first the large myelinated fibers.

3) May modify transmission in the dorsal horn (e.g. opioids: endorphin, enkephalin, dynorphin…). Opioids act on G-protein coupled receptors: Mu, Delta and Kappa. Opioid agonists reduce neuronal excitability (by increasing potassium conductance) and inhibit neurotransmitter release (by decreasing presynaptic calcium influx)

4) May affect the central component and the emotional aspects of pain (e.g. opioids, antidepressant). Problems of tolerance and dependence

Pathophysiologic Consequences of Unrelieved Pain

Physically and psychologically dangerous.

Immune system: decreasing natural killer cell number, function and activity. Can lead to death.

Pulmonary system: causing reflex muscle spasm leads to splinting which decreases pulmonary vital capacity, functional residual capacity.

Cardiovascular system: causing sympathetic over activity.

Gastrointestinal system: causing increased sympathetic activity, which increases GI secretions and smooth muscle sphincter tone decreases intestinal motility. Leads to gastric stasis and paralytic ileus.

Musculoskeletal system: Unrelieved pain causes segmental and supra segmental reflexes with increased muscle spasm leads to impaired muscle metabolism and to muscle atrophy.

Neuronal plasticity: Unrelieved pain causes primary and secondary hyperalgesia.

Psychologic consequences of unrelieved pain include anxiety, fear, depression, distress, and suffering, hopelessness, helplessness and a decreased will to live (wish for assisted suicide or euthanasia).

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http://www.acupuncturedoc.com/national.htm

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v421/n6921/full/421328a_fs.html

http://www.westons.com/comtensj.htm

Phantom limb pain

Phantom limb pain occurs among between 50 and 80 percent of amputees.

Phantom pain can occur anytime, from just after an amputation to years later. Its occurrence is not related to psychological factors, age, sex, location of the amputation, or reason for the amputation (e.g. trauma vs. disease).

What causes Phantom Pain ?

1. Prior experience with pain prior to amputation.

2. Incorrect surgical procedure.

3. Climatic conditions - changes in air pressure and temperature.

4. Stress.

5. Inactivity - Remaining in a relatively same position for long periods of time.

6. Periodic illness - Colds, flu, strep throat, infections, viruses can increase the level of phantom sensation.

REMEMBER - Increased blood flow to the amputated area will (in many cases) reduce the amount of pain.

REMEMBER - The easiest and worst way to combat phantom pain to fill yourself full of medication.

Phantom limb pain: during amputation under general anesthesia the spinal cord can still “experience” the insult produced by the surgical procedure and central sensitization occurs. To try to prevent it, local infiltration of anesthetics in the site of surgery. But studies show also rearrangement of cortical circuits (cortical region of the missing limb receives afferents from other site of the skin)

Phantom Pain intensity as a function of Cortical Reorganization.

Projected Pain: e.g., nerve 자극 : 그 nerve 가 innervate 한 지역의 pain 으로 느낌 compression of spinal nerve

Neuralgia: continuous irritation of a nerve or a dorsal root (chronic nerve damage)---> spontaneous pain

Deafferentation pain: motor cycle injury : dorsal root 가 pulled away from the spinal cord (brachial plexus avulsion) : burning or electric pain in the dermatomes corresponding to the denervated area. : because of the hyperactivity of dorsal horn neurons in the deafferented region of the spinal cord

: 치료 : surgical ablation of the superficial dorsal horn

Causalgia: (reflex sympathetic dystrophy syndrome) : activity of efferent fibers of the sympathetic nervous system following peripheral nerve injury ---> activation of damaged nociceptive afferents