PAIN The task of medicine is to preserve and

restore health and to relieve suffering.

Pain is an unpleasent sensation

Pain is universally understood as a signal of disease.

It is the most common symptom that brings a patient to a physician's attention.

PAINPain is divided into acute & chronic

Acute pain last less than one month, after the injury that produces it is healed

Chronic pain last more than one month, after the injury that produce the pain is healed.

PAIN Pain represents a “massive worldwide”

socio-economic impact

Pain is the main reason for medical consultation

Chronic pain treatment implies in US:

More than 2 million are incapacitated p/y

More than 100 million work days are lost p/y

The cost of medical, surgical, rehabilitation, especial devices is more than 70 billion dollars p/y.

Treatment of pain is one of the most remunerative business to drugs companies.

PAIN The function of the pain sensory system is to:

Detect Localize Identify tissue-damaging processes.

Important diagnostic clues used to evaluate the response to treatment are:

Quality Time course Location of a patient's pain complaint Location of tenderness

PAIN THE PAIN SENSORY SYSTEM

Pain is often described in terms of: Physical stabbing, burning, twisting, tearing, squeezing

Emotional reaction Terrifying, nauseating, sickening.

Pain has a duality characteristic

It is both a “sensation” and “emotion” Acute pain is associated with behavioral arousal and a

stress response with increased: Blood Pressure Heart rate Pupil diameter Plasma cortisol levels

PAINTHE PAIN SENSORY SYSTEM

DEFINITIONS

Noxious stimuli is an internal or external stimuli that could elicit the activation of “pain receptors” , this could be:

Chemical Mechanical Thermal Polymodal

Nociception is the perception of signals evoked by activation of nociceptors at the C.N.S. To provide information of tissue damage

PAINTHE PAIN SENSORY SYSTEM

DEFINITIONS Fast pain:

Is a short well localized sensation that is well matched to the noxious stimuli.

Starts & stops abruptly when stimuli is applied or removed.

Is strictly associated to the skin (Prick, sharp pain)

Transsmitted by A-Delta fibers

PAINTHE PAIN SENSORY SYSTEM

DEFINITIONS Slow pain:

Is a throbbing, burning or aching sensation, is poorly localized & less especifically related to the stimuli.

The onset has a long latency following the application of the stimuli.

The pain continues for hours or days after removal of the stimuli.

Is associated to cutaneous and deep tissues.

Is transsmitted by C fibers

PAINTHE PAIN SENSORY SYSTEM

DEFINITIONSNociceptors:

Specialized sensory receptors that provide information about tissular damage

Are “free nerve endings”, localized at the skin, underlying tissue and visceras

Nociceptors are the least differentiated of the sensory receptors, there are two types: Thermal or Mechanical & polymodal

PAINTHE PAIN SENSORY SYSTEM

DEFINITIONS Nociceptors:

There are two types:

Thermal or mechanical, associated with fast, sharp pricking pain transmitted on small diameter, thinly myelinated A-Delta fibers) Release excitatory amino-acid-glutamate (Fast EPSP)

Polymodal nociceptors, activated by variety of high intensity mechanical & thermal stimuli, transmitted slowly on small unmyelinated C fibers, release excitatory aminoacid-glutamate and neuropeptides (Substance P = slow EPSP)

Substances & effects on nociceptors

SUBSTANCES

Potassium Bradykinin

Substance P Serotonin Histamine Prostaglandins Leukotrienes

EFFECTS

Activation Activation &

sensitization Sensitization Activation Activation Sensitization Sensitization

Substances & effects on nociceptors

SUBSTANCES

Bradykinin

Substance P

Histamine

EFFECTS

Most potent pain produced agent

Vasodilator & Release Histamine

Activates polymodal nociceptors

PAINDEFINITIONS

Hyperalgesia:

Is the lowering of the threshold level of the nociceptors, after noxius stimuli is applied and there is tissular damage.

There is increased sensation of pain with subsequent stimuli

Is divided into:

Primary: occurs at the site of tissue damage

Secondary: increased sensitivity at the surrounding undamaged tissue

PAINDEFINITIONS

Primary hyperalgesia mechanism

Repetitive heating: reduces threshold of C & Alfa nociceptors

Repetitive mechanical stimuli: sensitize nearby nociceptors

Changes in synaptic efficacy of afferent fibers at spinal cord or C.N.S.

PAINDEFINITIONS

Secondary hyperalgesia mechanism

Sensitization of nociceptors with diffuse collateral branches, one of which innervates the site of injury

Sensitization of central nociceptors as a result of sustained activation

Suggested CNS facilitation of incoming pain stimuli

PAIN NOCICEPTOR-INDUCED INFLAMMATION

Released Substance P actions

Potent vasodilation

Degranulation of mast cells

Chemotaxis to leukocytes

Increase production and release of inflammatory mediators

Induces neurogenic formation

PAIN Pain ascending pathways.

Nociceptor

Pain fibers: A-Delta fibers C Fiber

Spinal cord relays Lamina I & II (Substantia gelatinosa) Synapsis to spinal neurons

Spinal neurons receives convergence imputs from many primary afferents. Upper and lower spinal cord level (Important for “refered pain”)

Spinal neurons send axons to contralateral spinothalamic tract

PAIN Pain ascending pathways.

Spinal cord relays send axons to contralateral spinothalamic tract

Spinothalamic tract axons connect to Thalamic neurons

Thalamic neurons projet to somatosensory cortex and cingulate gyrus and frontal lobe (Emotional responses)

Substances & effects at the spinal cord

Substance Main location or source

Effects on pain

transmition

Glutamate A delta & C fibers

Excitatory

Substance P C fibers Excitatory

Opioids Substantia gelatinosa

Inhibition

PAIN WHY THE DIFFERENT INDIVIDUAL RESPONSES

TO THE SAME NOXIOUS STIMULI OR TISSULAR DAMAGE??

Pain threshold is the same for everybody

The “Analgesia” system is involved in this individual response

It “modulates” (Increase or decrease) and sometimes suppress completely the transmition of the noxious stimuli

PAIN ANALGESIA SYSTEM

SUPRASPINAL ANALGESIA SYSTEM

Periaqueductal Gray matter Opioids

Raphe magnus nucleus Serotonin

Nucleus Paragiantocellularis Nor-epinephrine

Send the Dorsolateral funiculus that end at the dorsal horn of the spinal cord

PAIN SPINAL ANALGESIA SYSTEM

Dorsolateral funiculus;

Is a descending tract that end at the dorsal horn of the spinal cord inhibiting ascending spinothalamic projection neurons

Directly releases serotonin and nor-epinephrine

Indirectly through enkephalin interneurons in the dorsal horn

Local opioids Gate control theory Wide Dinamic Range Neurons

PAIN Special considerations on pain

Refered pain: Is the pain that arises from nociceptors in

deep visceral structures, but is felt at sites on the body surface, sometimes remote areas

Examples: Myocardial infarction pain Esophageal diseases Gall bladder disease Apendicitis Gastric diseases

PAIN Special considerations on pain

Deafferentation pain (Nerve elongation)

Limb phantom pain (Amputation)

Proposed mechanism: Loss of afferent input

plus Hyperactivity of dorsal neurons

PAIN Special considerations on pain

Sympathetically maintained Pain “Causalgia”

Chronic pain after peripheral nerve injury, accompanied by swelling of the extremity, periarticular osteoporosis, and arthritic changes in the distal joints.

Pathophysiology is poorly understood

Rapid pain relief could be achived by blocking sympathetic nervous system

PAIN TREATMENT

Peripheral analgesics

Acetaminophen

Aspirin

Non-steroidal Anti-inflammatory NSAIDs

COX 2 selective drugs (Rofecobix, celecobix)

Ketorolac

PAIN TREATMENT

Central analgesics

Opioids: Orally Sublingual Transdermal Parenteral Intra-spinal

Chronic use of opioids

Patient controled analgesia (PCA)

PAIN TREATMENT

Antidepresant drugs Tricyclic

Anticonvulsant Fenitoin Carbamazepine CBZ Gabapeptin

Antiarrhythmic Lidocaine Mexiletine