Central pain syndrome

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

The mechanisms of pain and the ability to control pain may vary in different pain states. This is of particular importance in consideration of a rational basis for the treatment of both inflammatory and neuropathic pain where the damage to tissue and nerve leads to alterations in both the peripheral and central mechanisms of pain signalling. In respect of existing drug therapies, this plasticity, the ability of the system to change in the face of a particular pain syndrome, explains the effectiveness of NSAIDs in inflammatory conditions and yet is also responsible for some of the limitations in the effectiveness of opioids in neuropathic pain. 

Features of central sensitization are pain in response to normally innocuous tactile stimuli, and the spread of pain sensitivity beyond the site of tissue injury. Central sensitization plays a major role in acute post-traumatic pain, and also in migraine, neuropathic pain (see below) and some diffuse chronic pain syndromes, such as fibromyalgia and irritable bowel syndrome. In these conditions, which have no detectable peripheral trigger, an autonomous central sensitization may be the pathology, increasing the gain in neuronal activity in the CNS and thereby producing abnormal responses to normal inputs. 

Pain resulting from non-inflammatory dysfunction of the peripheral or central nervous system without nociceptor stimulation or trauma. Examples include post-herpetic neuralgia, complex regional pain syndromes, phantom pain and trigeminal neuralgia. 

This ability to test drugs in contexts other than acute pain models has arisen from good communication between bench scientists, clinicians and industry. Until recently investigations into the mechanisms of clinical pain syndromes all relied on animal studies using acute stimuli. The symptoms of pain arising from nerve injury, neuropathic pain, such as allodynia, spontaneous pain, hyperalgesia, sensory deficits and in some cases a sympathetic component are simply not seen in the older acute models. There are now several animal models which mimic peripheral and central neuropathic states. The same is true for inflammation. 

These include postherpetic neuralgia, phantom limb pain, peripheral neuropathies of various causes, central pain, e.g. following a stroke, compression neuropathies, and the complex regional pain syndromes (comprising causalgia, when there is nerve damage, and reflex sympathetic dystrophy, when there is tissue but no nerve injury) they present the most challenging problems. 

Motor cortex stimulation is reserved for the treatment of complex central and neuropathic pain syndromes that have proven refractory to medical treatment, including post-stroke pain, deafferentation pain, and some neuropathic pain states of peripheral origin. 

In a patient with severe radicular pain and central cord syndrome, the addition of lamotrigine 100-200 mg/day over a period of 6 weeks reduced pain intensity scores from 100mm down to 20mm and greatly improved quality of life [6]. 

Antiepileptics are used in neuropathic pain resulting from lesions to the peripheral (e.g., diabetes, heipes) or central nervous system (e.g., stroke). Such syndromes have been attributed to ectopic activity in sensitized nociceptors from regenerating nerve sprouts, recruitment of previously silent nociceptors, and/or spontaneous neuronal activity. This may result in sensitization... 

Nociceptive neurons in the spinal cord as well as in higher centres such as the thalamus and cortex can also undergo alterations in activity following chronic peripheral changes and trauma (Table 1). These changes are typically long-term in nature and lead to the clinical syndromes of centrally maintained pain (secondary hyperalgesia, allodynia, spontaneous pain). Alterations... 

Neuropathic pain is defined as spontaneous pain and hypersensitivity to pain associated with damage to or pathologic changes in the peripheral nervous system as in painful diabetic peripheral neuropathy (DPN), acquired immunodeficiency syndrome (AIDS), polyneuropathy, post-herpetic neuralgia (PHN) or pain originating in the central nervous system (CNS), that which occurs with spinal cord injury, multiple sclerosis, and stroke. Functional pain, a relatively newer concept, is pain sensitivity due to an abnormal processing or function of the central nervous system in response to normal stimuli. Several conditions considered to have this abnormal sensitivity or hyperresponsiveness include fibromyalgia and irritable bowel syndrome. 

Tension-type headache (TTH) is the most common primary headache disorder. It is often underrepresented in clinical practice, as many patients do not present for care.6 The term tension-type headache is used to describe all headache syndromes in which muscle contraction is the most significant factor in the pathogenesis of pain. The 1-year prevalence of TTH in the population ranges from 30% to 90%.6 It is more common in adult females. Environmental factors, as opposed to genetic predisposition, play a more central role in their development. Tension-type headaches can be further divided into episodic or chronic the mean frequency of attacks is 3 days per month in episodic disorders, and chronic TTH is defined as 15 or more attacks in a 1-month period.7 The estimated prevalence of chronic TTH is less than 5%.6 Some researchers believe that chronic TTHs represent a continuum of headache severity with migraine headache.8 When severe headaches are difficult to differentiate clinically, treatment should initially target TTH. 

G. Other applications Limited data show some beneficial effects of leuprolide in the treatment of breast cancer. According to Micromedex, there is good documentation that leuprolide is effective for bowel pain and nausea associated with irritable bowel syndrome. Leuprolide has been used for controlled ovarian hyperstimulation to enhance the in vitro fertilization-embryo transfer procedure. In endometriosis, the goal of treatment is pain relief and reduction of endometriotic lesions. In children with central precocious puberty, stimulated and basal gonadotropins are reduced to prepubertal levels. Testosterone and estradiol are reduced to prepubertal levels in males and females, respectively. 

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