PAIN MANAGEMENT

presentation by Mariyam Nadeem4th year MBBS student

CONTENTS

Nociceptors Primary afferent nerves Secondary afferent nerves Pain pathways Mechanism of action of NSAIDs and

opoids

PAIN

Pain is an unpleasant sensation localized to a part of body.

It is often described in terms of peneterating or tissue destructive process(eg.,stabbing,burning,tearing) or of a bodily or emotional reaction(eg.,nauseating,terrifying)

Classification of pain Pain can be classified based on pain physiology, in

tensity, duration and syndrome: Pain physiology (nociceptive, neuropathic, inflam

matory) Intensity (mild-moderate-severe; 0-10 numeric pa

in rating scale) Time course (acute, chronic) Syndromes (cancer, fibromyalgia, migraine, other

s)

Primary afferent nerves

Primary afferent nerve fibres that transmit electrical impulses from the tissues to the spinal cord via the ascending nerve tracts.

The cell bodies of primary sensory nerves are located in the dorsal root ganglion in the vertebral foramina

It has two branches:i. one projects centrally into the spinal cordii. other projects peripherally to innervated tissues.

Classification of primary afferent nerves

Primary afferents are classified by their diameter,degree of myelination and conduction velocity

Basically divided into 3 classes

i. The largest diameter afferent fibers A-beta(responsd maximally to light touch or moving stimuli)

ii. The small diameter myelinated A-delta

iii. The small diameter unmyelinated C fiber axons

Pain receptors or nociceptors

Primary afferent nociceptors are specialized free nerve endings of primary afferent nerves (A-delta and C fibres).

They are generally the first structures to be involved in the nociceptive process and are located in various body tissues including skin, muscle, connective tissue, blood vessels and thoracic and abdominal viscera

The skin is supplied by A-delta and C-nociceptors/fibres. Muscles, joints, fasciae and other deep somatic structures are supplied mainly by C- but also some A-delta nociceptors/fibres.

Nociceptor induced inflammation Primary afferernt nociceptors also have neuroeffector

function Most nociceptors contain polypetide mediators that are

released from their peripheral terminals when they are activated.

An example is substance P,it has multiple biologic activities like

it is a potent vasodilator degranulates mast cells chemoattractant for leukocytes increase the production and release of inflammotory

mediators

A-delta nociceptors are activated by mechanical and thermal stimuli. Activation of A-delta fibres results in short-lasting, pricking-type pain

C nociceptors are polymodal (mechanical, thermal, chemical)

Activation of C fibres results in dull, poorly localized, burning type pain

Stimulation of these nociceptors occurs when the pain threshold is reached

This then results in propagation of impulses along the afferent fibres toward the dorsal horn of the spinal cord (periphery) or to the medulla (cranial).

Stimulation of the primary afferent nociceptors which result in pain can be from

1) Physical stimuli like mechanical injury, noxious heat, radiation etc 2) By products of tissue damage resulting in release of cellular content

s and chemical mediators from the nociceptive afferents.

Chemicals released from damaged cells include bradykinin, potassium, serotonin, histamine, cytokines, nitric oxide, hydrogen ions, prostaglandins, leukotrienes, slow reacting substance of anaphylaxis.

Mediators released from the afferent nociceptors include substance P, calcitonin-gene-related peptide, neurokinins.

After a brief period of noxious stimulation, peripheral sensitization occurs

Sensitization

When intense,repeated or prolonged stimuli are applied to damaged or inflamed tissue,the threshold for activating primary afferent nociceptors is lowered.

Inflammatory mediators such as bradykinin,prostaglandins and leukotrienes contribute to sensitization process.

Sensitization occurs at the level of the peripheral nerve terminal(peripheral sensitization) as well as at the level of the dorsal horn of the spinal cord(central sensitization).

Pain Threshold – The point at which a stimulus, usually one associated with pressure or temperature, activates pain receptors and produces a sensation of pain. Individuals with low pain thresholds experience pain much sooner and faster than those with higher thresholds

Pain Tolerance – amount of pain a person is willing or able to tolerate

Central mechanism(spinal cord)

Th axons of primary afferent nociceptors enter the spinal cord via the dorsal root

They terminate in the dorsal horn of the spinal gray matter

The terminals of primary afferent axons contact spinal neurons that transmit the pain signal to brain sites involved in pain preception

When primary afferents are activated by noxious stimuli,they release N.T(like glutamate) that excite the spinal cord neurons or secondary afferent neurons.

Pain pathways

Anterolateral or spinothalamic pathway

Anterolateral pathway

Pain & Temperature 3 neuron pathway. Its primary neurons axons enter the spinal cord and then ascend one to two

levels before synapsing in the substantia gelatinosa.

After synapsing, secondary axons decussate and ascend in the anterior lateral portion of the spinal cord as the spinothalamic tract.

This tract ascends all the way to the thalamus, where it synapses on tertiary neurons.

Tertiary neuronal axons then travel to the primary sensory cortex

MECHAINISM OF ACTION OF NSAID

NSAIDS

Nonsteroidal anti-inflammatory drugs are a class of drugs that provides analgesic (pain-killing) and antipyretic (fever-reducing) effects, and, in higher doses, anti-inflammatory effects.

The most prominent members of this group of drugs are aspirin, ibuprofen and naproxen.

Paracetamol (acetaminophen) is not considered an NSAID because it has only little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the CNS but not much in the rest of the body

Mechanism of action Most NSAIDs act as nonselective inhibitors of the

enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes.

COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2).

PGs directly stimulate pain receptors and increase sensitivity of pain receptor to bradykinin etc to produce pain . NSAIDs relieve pain via inhibition of PGs biosynthesis.

MECHAINISM OF ACTION OF OPOIDS AS ANALGESIC

Opoids Opioids interact with one or more subtypes of

opioid receptors (eg μ,κ,δ) at supraspinal, spinal and peripheral sites to produce analgesia and a multitude of other effects.

Current potent opioid analgesics are mu agonists, although specific delta and kappa agonists may also produce analgesia.

Types of opoids

Generic Name Brand Name fentanyl Duragesic hydrocodone Norco, Vicodin hydromorphone Dilaudid, Exalgo morphine Astramorph, Avinza oxycodone OxyContin, Percocet

Mechanism of action Opioids act by: • presynaptic inhibition of production of neurot

ransmitters C-fiber endings, • postsynaptic suppression of evoked activity in

nociceptive path. •Supraspinal opioids increase descending inhibi

tion of spinal nociceptive transmission.

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