Neuralgia
Diseases

Description

Neuralgia or neuropathic pain can be defined as non-nociceptive pain, or in other words, pain that is not related to activation of pain receptor cells in any part of the body. Neuralgia is pain produced by a change in neurological structure or function. Unlike nociceptive pain, neuralgia exists with no continuous nociceptive input. Neuralgia falls into two categories: central neuralgia and peripheral neuralgia. This unusual pain is thought to be linked to four possible mechanisms: ion gate malfunctions; the nerve becomes mechanically sensitive and creates an ectopic signal; cross signals between large and small fibers; and malfunction due to damage in the central processor.

Pathophysiologic mechanisms

Clinical investigations of pain mechanisms are labor intensive and require specialized equipment; thus, they are not yet practical for routine clinical use. Even in specialized pain research settings, it is difficult to identify specific neuropathic pain mechanisms. A simple focal peripheral nerve injury unleashes a range of peripheral and central nervous system processes that can all contribute to persistent pain and abnormal sensation. Inflammation , reparatory mechanisms of neural tissues in response to injury, and the reaction of adjacent tissues to injury lead to a state of hyperexcitability in primary afferent nociceptors, a phenomenon termed peripheral sensitization. In turn, central neurons innervated by such nociceptors undergo dramatic functional changes including a state of hyperexcitability termed central sensitization. Normally these sensitization phenomena extinguish themselves as the tissue heals and inflammation subsides. However, when primary afferent function is altered in an enduring way by injury or disease of the nervous system, these processes persist and may be highly resistant to treatment.
Injury or permanent loss of primary afferent fibers (deafferentation) differentiates peripheral neuropathic pain from other types of pain. Positive sensory phenomena (spontaneous pain, allodynia, and hyperalgesia) that are characteristic of patients with neuropathic pain are likely to have many underlying mechanisms, including ectopic generation of impulses as well as the de novo expression of neurotransmitters and their receptors and ion channels. Direct injury to central structures may permanently alter sensory processing, and in some patients it causes central neuropathic pain and dysesthesias. The mechanisms underlying central neuropathic pain, however, are still unclear.
A simplified but useful approach is to distinguish processes that involve the following: (1) increased primary afferent nociceptor firing ( as a result of abnormal collections of sodium channels in damaged peripheral nerve fibers, causing ectopic discharge); (2) decreased inhibition of neuronal activity in central structures ( due to loss of inhibitory neurons); and (3) altered central processing (central sensitization) so that normal sensory input is amplified and sustained.

Symptoms

• Nerve pain
• Pain located anywhere, usually on or near the surface of the body
• In the same location for each episode
• Sharp, stabbing pain that comes and goes (intermittent) or constant, burning pain
• No associated movement disorder
• No associated paralysis
• Various symptoms depending on the type of neuralgia

Type

Occipital Neuralgia
Neuritis - inflammation of a nerve.
Trigeminal neuralgia affectial facial areas.
Peripheral neuralgia
Sciatic neuralgia - another name for sciatica.
Occipital neuralgia - affecting the head
Intercostal neuralgia - affecting the ribs.
Postherpetic neuralgia - related to shingles
Glossopharyngeal neuralgia - affects the tongue and throat

Causes

• Certain drugs
• Chemical irritation
• Chronic renal insufficiency
• Diabetes
• Infections, such as shingles, syphilis, and Lyme disease
• Porphyria
• Pressure on nerves by nearby structures (for instance, tumors)
• Trauma (including surgery)
• Hyper excitability of the nerve fiber due to a poorly functioning of Na+/K+-ATPase .In general slow-conducting unmyelinated C fibers are more affected because it is easier to create an electrolyte imbalance in this kind of fiber.
• Swelling and irritation (inflammation)
• Vascular-nervous conflict that a vessel encircle a nerve ,as a result of compression, the nerves lose their myelin sheath and become more irritable(Trigeminal neuralgia - affectial facial areas.

Causes of ATP depletion wich may cause neuralgia

Hypoxia(medical)
Depletion of ATP is one of the consequences of ischemia and cellular hypoxia A partial reduction in the level of ATP results in a hyper excitability of nerve fiber. Decrease in Na+/K+-ATPase activity leads to a gradual Na+ accumulation. In general slow-conducting unmyelinated C fibers are more affected because it is easier to create an electrolyte imbalance in this kind of fiber(for their more expensive metabolism).

Herpes zoster
Postherpetic neuralgia is a neuralgia generally caused by the varicella zoster virus. By reducing the iron up-take and by enhancing the sequestration of free iron, animal cells will limit the iron availability for virus proliferation. Iron reduction causes cytochrome c reduction wich causes ATP depletion.

• Study correlated

Hypothyroidism

Hypothyroidism causes cytochrome c reduction. Cytochrome c is an essential component of the Respiratory Chain. Depletion of cytochrome c causes ATP reduction.

• Effect of hypothyroidism on expression of cytochrome and cytochrome c oxidase in heart and muscle during development.

proton pumps inhibitors

Respiratory Chain inhibitors

Anemia

• Iron deficiency
• B-12 deficiency

Components of the respiratory chain deficiency

• NAD
• FAD
• Coenzyme Q10
• Eme
• Copper

Weather(Joints Pain)

Changes of barometric pression

Hypothesis

• These particular conditions may causes swelling of the joints and it may be that the swelling irritates the nerves around the joints that sense the pain.

• Barometric pressure reduction produces a Po2 reduction which causes ATP depletion.In favor of this hypothesis we observed that in patients who have suffered trauma, there is a pain related to the change of the weather (barometric pression), probably because the reparation of damaged tissue with fibrotic tissue leads to a less oxygen perfusion .

By Andrea Schiaffino and Marco Garrone