T3 Systems CNS: Central Modulation and Sensitization, Disease, and Terminology PDF

T3 October 2024 T3 Systems CNS: Central Modulation and Sensitization, Disease, and Terminology CENTRAL (DESCENDING) MODULATION There are modifiers of afferent transmission as it travels from the tissues to the brain, e.g., local inhibition/gating in the d...

T3 October 2024 T3 Systems CNS: Central Modulation and Sensitization, Disease, and Terminology CENTRAL (DESCENDING) MODULATION There are modifiers of afferent transmission as it travels from the tissues to the brain, e.g., local inhibition/gating in the dorsal horn and filtering in the thalamus. These are examples of ascending modulation. The CNS has descending modulation mechanisms as well, also often called central modulation. While descending modulation is most often discussed in the context of pain, it can also be used to weaken or suppress sensory experience of other types of stimuli. Understanding of the descending mechanisms is still incomplete. One of the first major commenters on these phenomena was H. K. Beecher, a WW2 physician who noted how frequently wounded soldiers felt little or no pain, especially initially. The same has been observed of injured athletes in the heat of competition. The purpose of sensory experience is to bring attention to important matters, often because of a need for response (or else reflection). However, in the absence of value, or in the presence of other purpose or distraction, the sensory experience may be eliminated or weakened. At the brain level, parts of the cortex, the thalamus, the insula, the amygdala and the hypothalamus are all involved. They collaborate to release chemicals, primarily endogenous opioids called _______________ Endorphins and ________________ Enkephalins (the body’s 1/12  version of morphine or heroin). These endogenous opioids are communicated to a group of nuclei in the midbrain and brainstem. Dopamine is also involved. Activation of these nuclei (notably the midbrain’s periaqueductal gray area (PAG)) initiates a complex intercommunication process that results in the release of modulators from brainstem zones like the raphe nuclei. These modulators include neurotransmitters such as serotonin (5-HT), norepinephrine (NE) (AKA noradrenalin NA) and endocannabinoid substances such as anandamide, which is similar to THC. These modulators in turn act on neurons in the dorsal horn. They can: directly inhibit at the synapses where C and A-δ fibres are attempting to activate 2° spinothalamic tract neurons activate local inhibitory neurons to “close the gate”, and inhibit firing of the 2° neurons themselves. These local neurons primarily use GABA and glycine. Endorphins and enkephalins can also produce effects in the spinal cord. 2/12 Central Modulation Problems Because of the scale of the centres and pathways involved in the descending modulation mechanisms, they can be impaired by any number of traumatic and pathological causes. This means that________________________________________ Type of pathological pain or sensation can result from aberrant nociception ______________________________________________________________________ Or CNS analysis or from failure of central modulation mechanism or both ______________________________________________________________________. Beyond this complex reality, it is useful for health care practitioners to be aware that mood states/mental health, traumatic history and chronicity can all alter central modulation in ways that affect sensory experience. 3/12 Anxiety, Fear, Stress, Distress Numerous studies have shown that the more anxious a person is, the more intense their A physiologic stress response evoked experience of pain. The neurochemistry of by fear or perceived threat … elicits anxiety and stress, in other words, the the secretion of sympathetic predominance of sympathetic nervous catecholamines (epinephrine and system activation, enhances pain perception norepinepherine) and neuroendocrine and pain distress (suffering). hormones (cortisol) to promote survival Central modulation is rendered less effective. and motivate success. Cortisol … It’s complex because of the number of functions to mobilize glucose reserves individual physical and psychoemotional for energy and modulate inflammation. factors that come into play, especially if Cortisol also may facilitate the dysfunctional stress becomes entrenched consolidation of fear-based memories and when anxiety illness is present. for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (e.g., rumination, magnification, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain … Exaggerated psychological responses Central Sensitization (e.g., catastrophizing) following With central sensitization, signals coming maladaptive cognitive appraisals of from sensory receptors along 1 neurons are potential stressors as threatening may normal – and should cause no (or less) pain. exacerbate cortisol secretion and But at the dorsal horn of the spinal cord, they facilitate the consolidation of fear- are amplified, based memories of pain or non-pain- ___________________________ And by the time they reach the brain what related stressors; however, coping, Should have been turned right up ___________________________________ ba a message of pain cognitive reappraisal, or confrontation ____________________________________ of stressors may minimize cortisol ___________________________________. secretion and prevent chronic, Nociceptive signals can also be sent to the recurrent pain. Hannibal & Bishop brain from the 2° in the CNS with no stimulus 2014 from the peripheral 1° neurons. The term central sensitization is often used to describe situations where a person’s history of physical and/or emotional trauma creates hyperfacilitation of pain and other distressing symptoms along with reduced effectiveness of descending modulation. Over time, it becomes entrenched via causing altered neuron health and function, dysfunctional synapses and various changes in neurochemical production and function. 4/12  Chronic pain syndromes are interwoven with this reality. Central sensitization mechanisms can be complicated by ________________, Somatization meaning that the person is expressing mental or emotional distress as physical symptoms. Depression Anxiety, central sensitization and depression are interconnected and often present in varying degrees in the same person over time. Anxiety, pain and distress cause depression by depleting serotonin, dopamine, endogenous opioid and norepinephrine volumes in the CNS, _____________________________ __________________________________. Depression itself depletes them, and so creates its own difficult cycle. The fact that these same chemicals are involved in descending modulation means that their effectiveness in that role is reduced as an intrinsic aspect of depression, resulting in the pain and other physical discomfort symptoms that are part of the clinical presentation of depression. all neurochemicals that are used to restore and balance mood 5/12  NOCEBO AND PLACEBO There is a great deal of interest in placebo effects, and in their negative counterpart, nocebo effects. Placebo effects that reduce/suppress uncomfortable symptoms seem to work in large part by enhancing central modulation. There is a connection here to massage therapy, in that some researchers believe that massage’s effects have placebo components, especially via the therapeutic relationship, but also probably through effects of touch on the brain. 6/12 DAMAGE, PATHOLOGY The sensory perception challenges discussed so far involve normal circuitry in the peripheral and central nervous systems. There are numerous ways that damage and disease can add to the brain’s interpretation difficulties. The factors can range from neuron loss/scarring that would lower firing rate, through to inflammation, edema, chemicals released by damaged tissue, etc., that can cause intense, irritable firing patterns. These phenomena can occur anywhere along the pathways that carry transmission to the sensory cortex and often promote proximal depolarization confusion. Ischemia, compression and demyelination are additional factors that can cause interpretation challenges in ways already mentioned. They can also create transmission pattern asynchrony. For example, a cluster of demyelinated axons, as in multiple sclerosis, will transmit more slowly than same-function neurons that are intact. Rather than a smooth, synchronous arrival, say at the thalamus, the information arrives in disordered batches, producing a more baffling interpretation challenge that often results in the assignment of dysfunctional sensation experiences. The illustration below shows how a sensation can be activated without a stimulus when there is damage to a 1° neuron’s receptor or axon. This type of abnormal signal activation can occur anywhere in the sensory system. 7/12  COMPLEX REGIONAL PAIN SYNDROME II / CAUSALGIA Complex Regional Pain Syndrome II (CRPS II) (formerly known as Causalgia) is an example of a specific symptom caused by peripheral nerve damage. Occurring mostly with median, sciatic (tibial) and C8/T1 spinal nerve injuries, it reflects damage/irritation to the sympathetic vasomotor neurons within the affected nerve. It typically onsets several weeks after the originating damage. The primary symptom is an intense “burning” pain that usually has a “shooting” quality, often accompanied by erythema (reddening) of skin. Pressure and temperature (esp. heat) stimuli are most likely to trigger CRPS II, but almost any stimulus can be implicated, and guarding postures and behaviours become normal. Strong emotional states are also known triggers/aggravators. CRSPS I (formerly known as reflex sympathetic dystrophy) is a variant where the pain is not localized to the area around the injured peripheral nerve. Neuropathic Pain Neuropathic pain is a common phenomenon when there is irritation/damage in the sensory nervous system. The damage can be to peripheral nerves (trauma, neuralgias, shingles, facet joint issues, amputation etc.) or in various locations in the CNS (transverse myelitis, spinal 8/12  stenosis, multiple sclerosis, CNS infections, stroke etc.) or in both (alcoholism, diabetes, chemotherapy etc.). Possible cause factors are listed in the drawing below, illustrating the range of ascending and descending abnormalities that can play a role. 1. Sprouting of sympathetic post-ganglionic nerve fibres on 1 afferent endings and 1 sensory cell bodies 2. Lowered threshhold for firing of C fibres (hyperesthesia) and A delta fibres (allodynia) 3. Proliferation of alpha adranergic receptors on 1 sensory afferent endings and 1 cell bodies 4. Possible ephaptic afferent activation 5. Permanent hyperactivation of wide dynamic range neurons 6. Glutamate excitotoxic cell death of inhibitory neurons (glutamate storms) 7. Inadequacy of central descending serotonin, noroepinephrine, opioid peptide pathways to control nociception 8. Immobilization by pain decreases gating of nociceptive input, limiting physical therapy to initiate gating 9. Sprouting of C fibres in spinal cord 10. Extension of interneuron dendrites into additional spinal cord laminae 9/12  The presentation can vary substantially as well, from numb, tingling sensations to “burning” or “electric shock” or “stabbing” to more everyday types of pain, which can often be triggered by non-nociceptive stimuli. It may be continuous or more episodic. It is often severe and very challenging to live with. Fatigue, illness, intense emotional states, anxiety and depression can make it worse. The complexity of addressing neuropathic pain is illustrated in the range of treatment approaches recommended on WebMD: anticonvulsant, analgesic and antidepressant medications, physiotherapy, massage therapy, psychotherapy and acupuncture, as well as relaxation practices. CLINICAL TERMINOLOGY Massage therapists need to have a good grasp of the terms used to describe and record findings of sensory abnormalities. Some are very common and others less so, but all are likely to be encountered in massage practice at some time. Proper use of terminology leads to more effective communication with other practitioners, and also to the ability to read research, articles, and clinical reports of different types. Please note that these terms are purely descriptive of the sensory symptom. They do not inherently include a sense of what the cause is, nor indicate whether the problem is coming from the peripheral or central nervous system. Anaesthesia: ____________________________; Absence of any sensation the stimulus does not produce any of the expected sensation. Anaesthesia can also be induced, for example by using a nerve-blocking agent in dental work. __________________________: Hypeesthasia Diminished sensation; the experience matches the nature of the stimulus, but is less strong than expected. Hypaesthesia is colloquially referred to as numbness. The image on the right depicts the classic “sock and glove” sensory loss pattern in diabetes. The darker areas on the hands/ feet indicate anaesthesia and the rest of the shading, hypaesthesia. Hyperaesthesia: Heightened or exaggerated sensation; the experience accurately matches the stimulus, but produces an exaggerated or unexpectedly strong response. This can occur because of neuronal irritation or damage, but also for a range of psychoemotional reasons. 10/12 Paraesthesia: Abnormal sensations, e.g., ‘pins and needles’, ‘prickling’, ‘bugs crawling on skin’ – the sensation experienced does not correlate with the stimulus. There is in fact no reliable paraesthesia stimulus – it is not a naturally produced sensation; the stimulus is creating irritation or perception of it is being skewed. Paraesthesia can also occur when there is reduced blood flow to a nerve. Dysaesthesia: When a paraesthesic sensation is painful, it is called dysaesthesia, e.g. ‘hot pokers’, ‘electric burning’ or ‘feels like it’s on fire’; these are dramatically strange and painful types of sensory experience. 11/12  ________________: Allodynia Instead of the expected sensation, an innocuous stimulus (e.g. like a feather touch) results in pain, typically a “regular” sort of pain experience, e.g., achy or sharp. In other words, this is a usual sort of pain experience, but it is being created in response to a normally non-nociceptive stimulus; it results in a reduced pain threshold. Allodynia can be caused by local nerve damage/irritation, by problems in the CNS circuitry or appreciation centres, and also by poor central modulation. Hypalgesia: The response to a nociceptive stimulus is weak; can be seen as hypaesthesia of pain; the sensation is not as strong as predictable because of the stimulus. Hyperalgesia, AKA Hyperalgia: Heightened sensitivity to painful stimuli; the person experiences an unexpectedly strong pain intensity as compared to the predicted response to the stimulus; often there is a continuation of the pain after the stimulation has ceased, sometimes for quite an extended period; may be accompanied by strong subjective/emotional response. The image below shows how injury can change our perception of pain. Sensations that are painful may become more painful (hyperalgesia) and sensations that are normally innocuous may become painful (allodynia). 12/12