Pain

Physiology and Analgesics

Pain
I. Anatomy II. Theory III. Definitions IV. Analgesics V. Multi-modal treatment VI. Alternatives

2 classes of nerve cells

1. Glial (glue) cells Nourish and support nerve cells. 2. Nerve (neuron) cells sense and conduct information.

The cell bodies are located in:

1. Dorsal root ganglion (for peripheral nerves) 2. Trigeminal ganglion (for sensory information from the head).

anatomy

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Nerve Fiber Distribution

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Nociception
Nociception conscious perception of pain.
Widespread (somatic and visceral) Mechanical, chemical, thermal There are four physiologic processes involved. Nociceptors are specific receptors found in the periphery. These nociceptors have receptors on their surface that modulate sensitivity to stimulation: GABA, opiate, bradykinin, histamine, serotonin,
capsaicin

Generation of noxious stimuli

Transduced (1) by nociceptors peripherally (electrical translation of stimulus) Transmitted (2) via:
A-Beta A-Delta C fibers to the spinal cord where this information is Modulated

(3) and sent to the brain for Perception (4).

Sensory Neurons
A Beta fibers (A) large, myelinated, responsible for vibration and position. Terminate on Laminae III, IV and V. A Delta fibers (A) small, myelinated, responsible for prickling, localized pain. Terminate in Laminae I, V, X. C-fibers unmyelinated, large, responsible for unpleasant, long lasting pain. Terminate in lamina II.
Mechanisms of Pain and their therapeutic implication. Muir, W.M.

Gait Theory
Incoming pain can be gaited off by stimulating other fibers. C fiber pain can be reduced by stimulating A delta fibers, and also by stimulating A beta fibers (e.g. via rubbing skin).

Dorsal Horn

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Dorsal Horn Neurochemistry

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Neurotransmitters associated with Pain

Excitatory: Glutamate, substance P, neurokinin A, neurokinin B, calcitonin gene-related peptide, vasoactive intestinal polypeptide, somatostatin, bombesin Inhibitory:
Gamma amino butyric acid (GABA)

Neurotransmitters associated with Pain

Descending pain regulation:
Norepinephrine, serotonin, opiates

Laminae of spinal cord

Gray matter is divided into 10 laminae. Many pain transmitting fibers enter spinal cord at dorsal horn and synapse in laminae. I-V: receive most of these fibers Ventral horn: receives 40% of fibers Sensory impulses travel towards brain in the spinothalamic tracts

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Laminae of the spinal tract

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Perception of noxious stimuli

Some impulses travel to anterior and anterolateral horns to provoke segmental reflex responses. Other impulses travel to higher centers via the spinothalamic, spinoreticular tracts.
Results in suprasegmental and cortical responses.

Miller, R. Anesthesia (fourth edition)

Why Treat Pain?

Tissue damage results in the release of :
Prostaglandins, histamine, serotonin, bradykinin, sustance P.

Physiologic responses to injury and stress:

Pulmonary, cardiovascular, gastointestinal and urinary dysfunction may result, as well as impaired muscle metabolism, function and neuroendocrine and metabolic changes.

Segmental reflex responses

Associated with surgery:
Increased skeletal muscle tone, spasm associated with increased oxygen consumption, lactic acid production.

Stimulation of sympathetic neurons

Tissue injury/Stress can result in sympathetic stimulation. Physiologic responses include:
Tachycardia Increased SV Increased cardiac work Increased myocardial oxygen consumption Decreased GI and urinary tone

Suprasegmental reflex responses

Further increase in sympathetic tone and hypothalamic stimulation.
Metabolism and oxygen consumption are increased Apprehension and anxiety may accompany pain results in additional hypothalamic stimulation.

Cardiovascular and Pulmonary changes

Stimulation of sympathetic neurons: tachycarida, SV, cardiac work, myocardial oxygen consumption.

GI and urinary dysfunction

Nociceptive impulses from viscera and somatic structures can result in:
Ileus, nausea, vomiting following surgery Hypomotility of urethra and bladder

Neuroendocrine and metabolic changes

Suprasegmental reflex responses result in:
Increased sympathetic tone, hypothalamic stimulation, increased catecholamine and catabolic hormone secretion (cortisol, ACTH, ADH, GH, cAMP, glucagon, aldosterone, renin, angiotensin II. Decreased secretion of anabolic hormones (insulin, testosterone).

Neuroendocrine and metabolic changes

The effects of these changes include:
Na, H20 retention Increased blood glucose Free fatty acids Ketone bodies Lactate production Chronic change can result in a catabolic state with negative nitrogen balance.

Definitions
Allodynia Pain induced by normally innocuous stimuli. Chronic Pain A change in the nervous system that increases sensory inputs, resulting in physiologic, metabolic and immunologic alterations that can alter homeostasis and contribute to illness and death.

Acute to Chronic Pain

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Definitions
Clinical Pain intense or prolonged painful stimulus, abnormal sensitivity, lower threshold to noxious stimuli.
a. Hyperalgesia exaggerated response to pain b. Primary Hyperalgesia increased pain at the site of injury c. Secondary Hyperalgesia Increased pain, sensitivity beyond the site of injury. (due to central sensitization = increase in spinal neuron excitability)

Definitions
Phantom Pain Pain at the site of limb amputation. Believed to be generated by activity in afferent fibers activated by mechanical stimuli. NMDA (N-methyl Daspartate) receptors are factors involved in maintenance of post-amputation pain.

Definitions
Wind-Up Build up of chemical mediators in the spinal cord, in response to surgical manipulation resulting in tissue damage. Results in exaggerated painful response to non-painful stimulus. NMDA receptors are considered responsible for wind-up. (Ketamine is an antagonist at these sites).

Analgesics
Preventing perception of pain by targeting points along the pathway of nociception

Transduction
occurs at peripheral nerves Prevent with: Local blocks, NSAIDs, Opioids, Alpha 2s, in some situations Dissociatives (e.g. Ketamine on burns)

Transmission
propagation of nerve impulses through the nervous system (nerves to spinal cord). Prevent with: Local blocks, NSAIDs, Epidural

Modulation
occurs in the dorsal horn of the spinal cord Prevent with: Epidural Opioids or Alpha 2 agonists, dissociatives (Ketamine)

Perception
occurs in the brain = conscious perception. Prevent with: General anesthesia, systemic Opioids, Alpha 2 agonists

Multimodal
By using two or more analgesics at separate sites along the pathway of nociception. Decreases the amount of each analgesic, therefore reducing the side-effects.

New Ideas
Gene C-fos
Thought to be the most significant discovery in the field of pain. Gene produces the protein Fos which increases when an animal feels pain (considered to be a molecular marker for pain) C-fos likely involved in chronic pain. Nociceptive Cfiber stim. is the main stimul. For ITF (inducible transcription factors) production in the spinal cord.

Alternatives
Homeopathic medications, acupuncture, etc. New medications (Anticonvulsants, e.g. gabapentin, etc.) Consider analgesia before painful stimulus (e.g. Fentanyl patches) Consider what you would want in the same situation.