How does neuropathophysiology affect the signs and symptoms of spinal disease?

Transcription

1 1 How does neuropathophysiology affect the signs and symptoms of spinal disease? Kidd BL, Richardson PM. FROM ABSTRACT: Best Practices and Research Clinical Rheumatology January 2002;16(1):31-42 A complex relationship exists between back pain and the presence of spinal disease. Particularly in chronic situations, back pain and its behavioural and emotional consequences are as likely to reflect the influence of psychosocial factors as any underlying spinal pathology. Nevertheless, physical factors are clearly important and it is significant that whereas in normal discs only the outer third of the annulus fibrosus is innervated, a much more extensive innervation develops in the presence of degeneration. [Very Important] Inflammation, as evidenced by leukocyte infiltration and expression of inflammatory mediators, is associated with disc degeneration and serves to alter the neural responses resulting in local and referred pain. It is probable that similar inflammatory processes, as well as direct root compression, contribute to radicular symptoms following disc herniation. An appreciation of these mechanisms encourages the search for novel treatments and permits a more rational and effective use of existing strategies for relieving pain. THESE AUTHORS ALSO NOTE: 60% of patients with acute low back pain will recover within 10 days. 40% of patients with acute back pain and associated sciatica recover within 10 days. Back pain that persists for 3 6 months is considered to be persistent or chronic. Chronic back pain patients also commonly suffer from anxiety, depression, and other psychological disturbances.

2 The majority of patients with persistent low back pain have associated degenerative (spondylotic) disease, although there is very little correlation between radiological evidence of spondylosis and symptoms. 2 NOCICEPTIVE pain arises from tissue damage and inflammation. NEUROPATHIC pain arises from nerve injury. NEUROPATHIC pain responds poorly to NSAIDs and opioids. NOCICEPTIVE pain has two categories: 1) Pain arising from short-lived stimuli. This type of pain is from minor experiences of daily life. 2) Pain arising from tissue damage. NOCICEPTIVE pain arising from tissue damage causes three physiological responses: 1) Direct activation of nociceptors causing pain. 2) Modifies the response properties of the nociceptive neurons to subsequent stimulation, known as PERIPHERAL SENSITIZATION. [Very Important] Under these conditions relatively innocuous stimuli, such as movement within the normal range, now produce pain. [Very Important] 3) The increased firing of the peripheral nociceptors leads to substantial changes in the function and activity of central pain pathways, known as CENTRAL SENSITIZATION. The enhanced responsiveness leads to exaggerated pain responses (HYPERALGESIA), tenderness and referred pain in areas away from the site of injury. It also leads to pain in response to trivial non-injurious stimuli, known as ALLODYNIA. NEUROPATHIC pain arising from peripheral nerve injury causes three physiological responses: 1) Abnormal function of the sodium ion channel at the site of nerve injury (creating a site of ectopic input), leading to increase input to the central nervous system, increasing pain, paresthesias, etc. 2) [Recall the post-ganglionic sympathetic efferent neuron releases the neurotransmitter norepinephrine, which alters neurophysiology by coupling with the adrenoreceptor]. If the peripheral nerve injury results in abnormal function (or expression) of the adrenoreceptor, it can lead to sympathetically maintained pain [reflex sympathetic dystrophy, complex regional pain disorder].

3 3) Abnormal neural sprouting [synaptogenesis / neuroplasticity] in the dorsal horn. This structural change significantly alters nociceptive traffic. SUMMARY: THREE CATEGORIES OF PAIN: 1) NOCICEPTIVE pain elicited by noxious stimulation of normal tissue. 2) NOCICEPTIVE pain from damaged or inflamed tissue. Exaggerated pain from a noxious stimulus (HYPERALGESIA). Pain from a non-painful stimulus (ALLODYNIA). 3) NEUROPATHIC pain from damaged or inflamed nerves. Have both HYPERALGESIA and ALLODYNIA. Also commonly display spontaneous pain. REFERRED PAIN 1) Is NOCICEPTIVE pain because it requires stimulation of peripheral receptors. 2) Is felt deep within the body with margins that are hard to localize. 3) Occurs because multiple primary order sensory neurons converge and use a common second order spinal cord afferent neuron. RADICULAR PAIN 1) Is NEUROPATHIC pain because it occurs as a result of sensory fibers being ectopically stimulated, resulting in symptoms being perceived as arising in the territory supplied by the affected fibers. 2) Its quality is lancinating and tends to have other sensory abnormalities, such as paraesthesia. 3) Is felt on the skin as well as deeply in the body. SEVEN MECHANISMS CONTRIBUTING TO PAIN TRAVELING TO THE BRAIN: 1) Nociceptor activation. 2) Peripheral sensitization of nociceptors from tissue damage or inflammation. 3) NEUROPATHIC ectopic discharge of nociceptors. 4) Central sensitization, which allows previously suppressed neurons into transmitting nociceptive information. 3

4 5) Loss of segmental pain inhibition. 4 6) Loss of descending pain inhibition. 7) Structural changes in neurons and synaptic connections [synaptogenesis / neuroplasticity]. Back pain is commonly present in the absence of identifiable spinal disease. Patients with disc disease or other spinal pathology may have no pain. Pain is a subjective experience that is always unique for each individual. There is no correlation between the severity of osteoarthritis and symptom intensity. There is no single pain pathway, but a series of parallel pathways bringing nociceptive information to the brain. The outer annulus of the disc is innervated. The NORMAL inner annulus of the disc and the nucleus is not innervated. Biopsy of degenerated discs for chronic pain patients shows nociceptive and sympathetic nerve fibers extending into the inner annulus and occasionally into the nucleus. [Important] The facet joint capsules, the facet joint synovium, the longitudinal ligaments, and the spinal dura can all produce pain. Inflammation alters the nociceptive threshold so that the pain neuron becomes activated at a lower threshold, as in a sunburn. This is important in chronic pain conditions. The smaller diameter unmyelinated C pain fibers are primarily sensitive to chemicals. There are three pathways for nociception to the brain: 1) The spinalthalamic tract. This pathway is important in the localization and characterization of pain. 2) The spinalreticular tract. 3) The tract to the parabrachial area of the brainstem. This pathway is most important in chronic pain syndromes.

5 This pathway has projections to the hypothalamus and amygdala, affecting emotional responses. 5 Lymphocytes and macrophages are present in herniated disc fragments. These lymphocytes and macrophages produce proteins called cytokines. These cytokines can directly sensitize the nociceptors, or indirectly sensitize them by stimulating the release of proinflammatory prostaglandins [PGE2]. Prostaglandins are important mediators of inflammation, fever, and pain. Prostaglandins are synthesized by COX enzymes, and COX enzymes can be produced by cytokines. Herniated disc material shows high levels of prostaglandin E2 (PGE2). An increased magnitude of inflammatory response in the disc lengthens the duration of the disease. [This is why it is important to reduce PGE2 derived inflammation in patients] Discogenic radicular syndromes include limb pain exacerbated by coughing, straining, and root stretch, and weakness / paresthesia in the root distribution. Radicular symptoms can be produced by direct compression of the nerve root. Radicular symptoms can also be caused by nerve root inflammation in the absence of compression. The dorsal root ganglion is more sensitive to mechanical stimulation than are the nerve roots. NEUROGENIC CLAUDICATION is the compression of the cauda equina from degenerative stenosis causing back or leg pain that is exacerbated by walking or standing and relieved by lumbar flexion. The most plausible explanation for the symptoms of NEUROGENIC CLAUDICATION is NOT ischemia, but from postural changes in intradural pressure. Intradural pressure is reduced in flexion. Both the neural canal and neural foramen are diminished by axial loading and with extension. CONCLUSION It seems probable that degenerative lumbar disc disease and associated disc herniation is associated with the presence of inflammatory cells and the production and release of inflammatory mediators. Inflammation is associated with disc degeneration.

6 There is much more extensive innervation present in the disc that has degeneration. 6 KEY POINTS FROM DAN MURPHY 1) In normal discs only the outer third of the annulus fibrosus is innervated, and a much more extensive innervation develops in the presence of degeneration, including into the nucleus. 2) Inflammation is associated with disc degeneration and alters the neural responses resulting in local and referred pain. 3) Both direct root compression and inflammatory processes contribute to radicular symptoms following disc herniation. 4) Chronic back pain patients also commonly suffer from anxiety, depression, and other psychological disturbances. 5) The majority of patients with persistent low back pain have associated degenerative (spondylotic) disease, although there is very little correlation between radiological evidence of spondylosis and symptoms. 6) THERE ARE THREE CATEGORIES OF PAIN: 6A) NOCICEPTIVE pain Type #1: This is normal pain that tells us that we have stressed our tissues. It is not associated with tissue damage or inflammation. 6B) NOCICEPTIVE pain Type #2: This is pain from damaged or inflamed tissue. These patients have an exaggerated pain from a stimulus, called HYPERALGESIA, and experience pain from a non-painful stimulus, called ALLODYNIA. 6C) NEUROPATHIC pain is from damaged or inflamed nerves. These patients also have both HYPERALGESIA and ALLODYNIA, and they commonly display spontaneous pain. 7) REFERRED PAIN is NOCICEPTIVE pain because it requires stimulation of peripheral receptors. 8) RADICULAR PAIN is NEUROPATHIC pain because it occurs as a result of sensory fibers being ectopically stimulated. 9) Back pain is commonly present in the absence of identifiable spinal disease. 10) Patients with disc disease or other spinal pathology may have no pain. 11) Pain is a subjective experience that is always unique for each individual.

7 12) The disc, the facet joint capsules, the facet joint synovium, the longitudinal ligaments, and the spinal dura can all produce pain. 7 13) Inflammation lowers the nociceptive threshold, as in a sunburn. 14) Lymphocytes and macrophages are present in herniated disc fragments and produce proteins called cytokines. Cytokine proteins can directly sensitize the nociceptors, or indirectly sensitize them by stimulating the release of proinflammatory PGE2. 15) Prostaglandins are synthesized by COX enzymes, and COX enzymes can be produced by cytokines. 16) Herniated disc material shows high levels of prostaglandin E2 (PGE2). 17) An increased magnitude of inflammatory response in the disc lengthens the duration of the disease. [This is why it is important to reduce PGE2 derived inflammation in patients] 18) NEUROGENIC CLAUDICATION is the compression of the cauda equina from degenerative stenosis causes back or leg pain that is exacerbated by walking or standing and relieved by lumbar flexion. THIS ARTICLE SUGGESTS THE FOLLOWING MODEL FOR DISC PAIN: Disc degeneration and herniation is associated with inflammation. Disc cell injury releases proinflammatory prostaglandin E2 (PGE2). Inflammatory PGE2 attracts lymphocytes and macrophages. Lymphocytes and macrophages produce proteins called cytokines. These cytokines are both inflammatory themselves, and they increase the production and activity of COX enzymes. COX enzymes increase the production of proinflammatory PGE2 from the omega-6 fat arachidonic acid, creating a positive feedback loop. The now increasingly inflamed disc alters the firing threshold of the disc nociceptors, sending pain signals to the brain. Because inflammation is involved, the disc can display both HYPERALGESIA and ALLODYNIA, initiating pain from normal activities of life that would normally not be painful. The inflamed and painful disc then structurally alters its own innervation, sending nociceptive fibers deeper into the annulus and even into the nucleus, further sensitizing the disc to initiate pain.

8 Linoleic Acid 18:2n-6 Corn, Cottonseed, Sunflower, Safflower, Peanut, Soy, Canola 8 PGE1 Activated By Insulin DiHomoGammaLinolenic Acid DHGLA 20:3n-6 Delta-5-desaturase D5D Inhibited By EPA Cox 1 Arachidonic Acid AA 20:4n-6 Cox 2 Cox 3 Prostaglandin E2 Increase SNS Production of CAs Fibrosis PGE2 #2 cause of INFLAMMATION Free Radicals Pain DJD Vascular Immune Disease System Dysfunction Increased IgE Reduced IgG

9 9 Alpha-Linolenic Acid ALA 18:3n-3 Flax, Hemp, Walnut Eicosapentaenoic Acid EPA 20:5n-3 Cold Water Fatty Fish Powerfully Anti-Inflammatory PGE3 Docosahexaenoic Acid DHA 22:6n-3 Cold Water Fatty Fish Algae Oil Source Builds Brain Synapses Increases Production of Serotonin, Dopamine