Chronic pain and Chronic pain syndromes

Question 1

What is chronic pain?

Answer 1

Chronic pain is any pain lasting longer than three months. It can be persistent, transient, or recurrent, and may require long-term medical management.

Question 2

What are the three categories of chronic pain syndromes based on pathophysiology

Answer 2

Chronic pain syndromes are categorized as:

Nociceptive pain (e.g., osteoarthritis).

Neuropathic pain (e.g., complex regional pain syndrome).

Nociplastic pain (e.g., fibromyalgia).

Question 3

What is nociceptive pain?

Answer 3

Nociceptive pain is pain that arises from tissue damage or inflammation, such as in osteoarthritis. It is often described as aching or throbbing and is typically well-localized

Question 4

What are common examples of nociceptive pain?

Answer 4

Examples of nociceptive pain include pain from arthritis, burns, fractures, and muscle injuries.

Question 5

What is neuropathic pain?

Answer 5

Neuropathic pain results from a lesion or disease within the somatosensory system, such as nerve damage, and often occurs spontaneously without external stimuli. It is commonly described as burning, shooting, or electric-like pain.

Question 6

What is nociplastic pain?

Answer 6

Nociplastic pain involves sensory alterations in nociception without any detectable lesion or nociceptive source, such as in fibromyalgia syndrome. It is characterized by pain sensitivity, widespread pain, and associated symptoms like fatigue and sleep disturbances.

Question 7

How can chronic pain be classified based on its duration?

Answer 7

Chronic pain can be classified as persistent (lasting continuously), transient (comes and goes), or recurrent (repeated episodes).

Question 8

What are examples of chronic pain syndromes ?

Answer 8

Examples include neuropathic pain, headaches, musculoskeletal pain (e.g., osteoarthritis, low-back pain), irritable bowel syndrome (IBS), burning mouth syndrome, and temporomandibular disorder (TMD).

Question 9

Where can neuropathic pain originate?

Answer 9

Neuropathic pain can originate from lesions in either the central nervous system (brain or spinal cord) or peripheral nerves

Question 10

What are the major causes of peripheral neuropathic pain?

Answer 10

Peripheral neuropathic pain can be caused by demyelination (loss of the myelin sheath), axotomy (cutting the nerve), or inflammation of peripheral nerves.

Question 11

What happens during axotomy

Answer 11

During axotomy, the cut nerve forms an end bulb, loses myelin, and sends out new sprouts. If the gap is too large, sprouts form a tangled knot called a neuroma, which generates ectopic potentials causing pain

Question 12

What is the ectopic firing hypothesis of neuropathic pain?

Answer 12

The ectopic firing hypothesis suggests that pain results from hyperexcitability at sites where myelin is lost, leading to spontaneous or evoked action potentials due to an accumulation of sodium channels and a decrease in potassium channels.

Question 13

How do A-delta and C-fibers differ in ectopic firing?

Answer 13

A-delta fibers exhibit rhythmic firing at higher frequencies (15-30 Hz), whereas C fibers fire at lower, irregular frequencies (1-10 Hz). Both types can be affected by external stimuli, causing after-discharges.

Question 14

What do thermal stimuli play in ectopia?

Answer 14

Cooling enhances ectopia in C fibers but reduces it in A -delta fibers, while warming has the opposite effect. This difference can be used therapeutically to manage neuropathic pain.

Question 15

How do adrenergic hormones affect ectopic firing?

Answer 15

Adrenaline and noradrenaline increase ectopic firing by enhancing neuroma sensitivity to adrenergic mediators, leading to heightened pain sensitivity. This effect can contribute to the persistence of neuropathic pain.

Question 16

Where else can ectopic firing occur besides the injury site?

Answer 16

Ectopic firing can also occur in the dorsal root ganglion (DRG) cell bodies of affected nerve fibers, which can contribute to shooting pain, altered pain behaviors, and spontaneous pain

Question 17

How does ectopia contribute to dorsal horn sensitisation?

Answer 17

Ectopic activity drives sensitization of dorsal horn neurons within minutes of nerve injury, leading to heightened pain processing and increased pain perception.

Question 18

What are common symptoms of neuropathic pain?

Answer 18

Symptoms include burning, searing, tearing pain, hyperalgesia (increased pain response), allodynia (pain from non-painful stimuli), tingling (pins and needles), dysesthesia (unpleasant sensations), decreased muscle tone (hypotonia), and motor incoordination (apraxia).

Question 19

What is peripheral neuropathy?

Answer 19

Peripheral neuropathy is a condition involving damage to peripheral nerves, leading to numbness, spontaneous pain, impaired sleep, drowsiness, fatigue, and other associated symptoms.

Question 20

What are the main types of peripheral neuropathy?

Answer 20

Peripheral neuropathy can be metabolic (e.g., diabetes), hereditary (e.g., Fabry’s disease), inflammatory (e.g., Guillain-Barré syndrome), nutritional (e.g., beriberi), or infectious (e.g., HIV)

Question 21

What is diabetic polyneuropathy

Answer 21

Diabetic polyneuropathy is a common complication of diabetes, where high sugar levels damage small nerve fibers and vascular tissues, leading to numbness, tingling, spontaneous deep aching pain, and foot ulcers

Question 22

How does diabetic polyneuropathy develop?

Answer 22

High blood sugar levels cause damage to small nerve fibers in distal areas like the feet. Damage to blood vessels also causes local anoxia (low oxygen), worsening the condition and contributing to ulcers.

Question 23

What is Fabry’s disease

Answer 23

Fabry’s disease is a hereditary polyneuropathy due to a deficiency in the enzyme alpha-galactosidase, causing accumulation of lipids and leading to burning pain in hands and feet. It primarily affects males, though it can affect females later in life.

Question 24

What is Guillain-Barre syndrome?

Answer 24

Guillain-Barré syndrome is an inflammatory demyelinating polyneuropathy caused by the Epstein-Barr virus, leading to early pain, motor weakness, demyelination of nerve roots, and possible need for ventilatory support.

Question 25

What is nutritional neuropathy (beriberi)?

Answer 25

Beriberi is caused by a deficiency of vitamin B1 (thiamine), leading to nerve degeneration, burning or lancinating pain in feet, and can be treated with B1 supplementation.

Question 26

What is HIV-associated neuropathy?

Answer 26

HIV-associated neuropathy affects about 30% of patients with AIDS, leading to burning pain, allodynia, and hypoesthesia due to vascular deficiencies and demyelination, which may be caused by HIV or antiretroviral drugs.

Question 27

What is low-back pain and its classifications?

Answer 27

Low-back pain affects the lumbar region and can be classified as: Axial pain - related to trauma or repetitive motion. Radicular pain - caused by compression of a nerve root (e.g., sciatica). Referred pain - resulting from degenerative disc disease, which may cause pain in areas like the hips or thighs.

Question 28

How is low-back pain categorised based on duration?

Answer 28

Low-back pain is categorized as: Acute: Lasting less than 6 weeks. Subacute: Lasting between 6-12 weeks. Chronic: Lasting more than 12 weeks.

Question 29

What are the risk factors for developing low-back pain?

Answer 29

Risk factors for low-back pain include obesity, smoking, sedentary lifestyle, physically demanding jobs, trauma, and psychological factors like anxiety and depression.

Question 30

How is low-back pain treated

Answer 30

Treatments include patient education, remaining active, using heat, topical analgesia, NSAIDs, and muscle relaxants. Chronic cases may require multidisciplinary treatment involving medical, psychological, physical, and interventional approaches.

Question 31

What are "red flags" and "yellow flags" in low-back pain?

Answer 31

Red flags are signs of serious underlying issues needing further evaluation (e.g., fractures, tumors), while yellow flags are psychosocial factors that increase the risk of chronic pain, such as anxiety, depression, fear avoidance behaviors, and catastrophizing.

Question 32

What is Complex Regional Pain Syndrome

Answer 32

CRPS is a type of neuropathic pain involving severe, persistent pain often following an injury. It includes symptoms such as swelling, skin color changes, temperature sensitivity, and decreased mobility of the affected limb.

Question 33

What are the phases of central sensitisation in neuropathic pain?

Answer 33

Central sensitization involves an initial phase where wide-dynamic range neurons are activated (wind-up), followed by long-term potentiation that prolongs neuron excitability and sensitization, leading to increased pain perception.

Question 34

How can chronic pain affect psychological well-being?

Answer 34

Chronic pain can lead to anxiety, depression, sleep disturbances, reduced quality of life, social withdrawal, and increased dependency on medications, requiring comprehensive pain management strategies.

Question 35

What is the role of cognitive behavioural therapy, CBT in chronic pain management?

Answer 35

CBT helps patients manage chronic pain by addressing negative thought patterns, promoting coping strategies, reducing anxiety and depression, and encouraging active participation in daily activities.

Question 36

What is the significance of patient education in managing chronic pain?

Answer 36

Patient education is crucial in managing chronic pain as it helps patients understand their condition, set realistic goals, adopt effective coping strategies, and improve adherence to treatment plans.

Question 37

How does physical therapy help in managing chronic pain?

Answer 37

Physical therapy helps improve mobility, strengthen muscles, reduce stiffness, and alleviate pain, thereby enhancing overall physical function and quality of life in

Question 38

What is failed-back surgery syndrome (FBSS)?

Answer 38

Failed-back surgery syndrome is a condition where patients continue to experience low back pain after one or more technically successful spinal surgeries. Symptoms include shooting, burning pain, and frequent allodynia.

Question 39

What are some risk factors for developing failed-back surgery syndrome?

Answer 39

Risk factors for failed-back surgery syndrome include preoperative anxiety, depression, poor coping strategies, pursuing litigation or workers' compensation, poor surgical technique, and postoperative complications like epidural fibrosis and new instability.

Question 40

What are the common intraoperative and postoperative factors that contribute to FBSS?

Answer 40

Intraoperative factors include poor surgical technique and incorrect surgery site, while postoperative factors include complications such as epidural fibrosis, new instability, and myofascial pain syndrome.

Question 41

What is complex regional pain syndrome (CRPS)?

Answer 41

Complex regional pain syndrome is a chronic pain condition characterized by spontaneous and evoked regional pain, usually beginning in a limb extremity after an injury, such as a fracture or surgery. It often includes autonomic changes, such as skin color and temperature changes, oedema, and sweating.

Question 42

What are the two types of complex regional pain syndrome?

Answer 42

CRPS is divided into Type I (reflex sympathetic dystrophy) with no major nerve injury and Type II (causalgia) with signs of major peripheral nerve injury. Both types share core diagnostic features.

Question 43

What are the characteristics of warm and cold CRPS?

Answer 43

Warm CRPS is associated with a warm, red, and swollen extremity, typically seen in acute cases, whereas cold CRPS involves a cold, dusky, sweaty extremity, often seen in chronic cases.

Question 44

What are some signs of autonomic and inflammatory changes in CRPS?

Answer 44

Signs include skin color changes, temperature differences between limbs, altered sweating, oedema, abnormal hair, skin, or nail growth, and reduced strength and proprioception.

Question 45

What are some potential mechanisms involved in the development of CRPS?

Answer 45

CRPS involves both peripheral and central mechanisms, including peripheral sensitization of primary afferent fibers, central sensitization in the spinal cord, and altered function of the sympathetic nervous system.

Question 46

How might the immune system be involved in CRPS?

Answer 46

Recent studies suggest that antibodies from individuals with CRPS may contribute to the condition, indicating a possible autoimmune component.

Question 47

What brain changes have been observed in CRPS patients?

Answer 47

Brain imaging studies show impaired pain inhibitory pathways, reduced limb representation in somatosensory cortices, and alterations in the primary and secondary somatosensory areas.

Question 48

How do psychological factors influence CRPS?

Answer 48

Although psychological factors do not cause CRPS, factors like anxiety, depression, and anger may exacerbate symptoms, potentially through effects on sympathetic nervous system arousal and catecholamine release.

Question 49

What is trigeminal neuralgia?

Answer 49

Trigeminal neuralgia is a condition causing electric shock-like pain on one side of the face, usually in the two lower branches of the trigeminal nerve. It is often provoked by light touch and can interfere significantly with daily activities.

Question 50

What causes trigeminal neuralgia?

Answer 50

Trigeminal neuralgia is typically caused by vascular compression of the trigeminal nerve root, though it can also result from brain tumors, multiple sclerosis, or vascular anomalies.

Question 51

What is the ignition hypothesis in trigeminal neuralgia

Answer 51

The ignition hypothesis suggests that trigeminal neuralgia results from a combination of central demyelination of the nerve root entry zone and reinforced electrical excitability.

Question 52

What is Phantom Limb Pain (PLP)

Answer 52

Phantom limb pain is pain felt in a limb that has been amputated, often described as cramping, burning, or shooting. It can occur in up to 80% of amputees and often starts within the first week after amputation

Question 53

What are the key areas implicated in the development of phantom limb pain?

Answer 53

The key areas implicated include peripheral nerves (due to sensitization and inflammation), the spinal cord (involving NMDA receptor-mediated changes), and the somatosensory cortex (with cortical reorganization).

Question 54

How do peripheral nerves contribute to phantom limb pain

Answer 54

Peripheral nerve injury leads to the release of pro-nociceptive factors, such as cytokines and substance P, which decrease activation thresholds and cause spontaneous discharge, contributing to phantom limb pain.

Question 55

What changes occur in the spinal cord that contribute to phantom limb pain?

Answer 55

Intense nociceptive input leads to changes in NMDA receptor activity, phenotypic switching, and cross sprouting, resulting in increased sensitivity and pain perception even beyond the original site of the limb.

Question 56

What role does the somatosensory cortex play in phantom limb pain?

Answer 56

After amputation, compensatory cortical migration occurs, where adjacent regions of the somatosensory cortex invade the area representing the missing limb, leading to phantom sensations and pain.

Question 57

How might phantom pain be triggered by stimuli to other body parts?

Answer 57

Due to cortical reorganization, stimuli to areas like the face (for upper limb amputees) or a full bladder (for lower limb amputees) may trigger phantom limb pain.

Question 58

What is the difference between warm and cold CRPS in terms of pathophysiology

Answer 58

Warm CRPS is associated with proinflammatory responses and vasodilation, while cold CRPS involves vasoconstriction and altered sympathetic nerve control, often leading to reduced blood flow and increased pain.

Question 59

What are the treatment challenges for patients with failed-back surgery syndrome?

Answer 59

Treatment is challenging due to the presence of persistent pain despite technically successful surgery, requiring multimodal approaches including pain medications, physical therapy, psychological support, and possibly further surgical intervention.

Question 60

How is CRPS diagnosed?

Answer 60

CRPS is diagnosed based on clinical features, including disproportionate pain, autonomic signs (e.g., temperature changes, sweating), motor dysfunction, and changes in skin, hair, or nail growth in the affected limb.

Question 61

What are some therapeutic approaches to managing CRPS?

Answer 61

Management includes physical therapy, medications (e.g., NSAIDs, corticosteroids, bisphosphonates), sympathetic nerve blocks, psychological interventions, and emerging therapies like immune-modulating treatments.

Question 62

What are the characteristic pain descriptors used by patients with phantom limb pain?

Answer 62

Patients often describe phantom limb pain as cramping, burning, shooting, or feeling like nails are being pulled from nail beds. Pain can also involve a twisted or cramped sensation in the missing limb.

Question 63

What factors increase the risk of developing phantom limb pain?

Answer 63

Factors include pre-amputation pain, significant neural trauma, and a history of psychological risk factors such as anxiety or depression, which can lead to more severe and disabling phantom pain.

Question 64

How does the NMDA receptor contribute to phantom limb pain?

Answer 64

The NMDA receptor is involved in central sensitization, modifying nociceptive signals and facilitating CNS plasticity, which contributes to increased sensitivity and the perception of phantom limb pain.

Question 65

What are some emerging theories on the immune system's involvement in CRPS?

Answer 65

Emerging theories suggest that CRPS may involve autoimmune processes, supported by evidence that antibodies from CRPS patients could transfer symptoms to unaffected individuals.

Question 66

How does cortical reorganisation influence the experience of phantom limb pain?

Answer 66

Cortical reorganization involves the migration of sensory representation into the area of the missing limb, causing phantom sensations. For example, touching the face may trigger phantom pain in an upper limb amputee.

Question 67

What is myofascial pain syndrome, and how does it relate to failed-back surgery syndrome?

Answer 67

Myofascial pain syndrome is characterized by muscle sensitivity and pain that can develop after spinal surgery, contributing to continued pain in failed-back surgery syndrome.

Question 68

What role does sympathetic nervous system dysfunction play in CRPS?

Answer 68

Dysfunction in the sympathetic nervous system can lead to abnormal vasoconstriction and sensitivity to circulating catecholamines, contributing to the autonomic and inflammatory symptoms of CRPS

Question 69

What is post-herpetic neuralgia (PHN)

Answer 69

Post-herpetic neuralgia (PHN) is chronic pain lasting more than three months that occurs after a herpes zoster (shingles) infection, affecting the distribution of one or more sensory roots involved in the infection.

Question 70

What causes post-herpetic neuralgia (PHN)

Answer 70

PHN results from the reactivation of varicella zoster virus (VZV), which remains dormant in sensory ganglia after the primary chickenpox infection. Reactivation occurs due to weakened cell-mediated immunity from disease, immune suppression, or cancer treatments.

Question 71

What are the common symptoms of PHN?

Answer 71

PHN pain can be continuous or intermittent, deep or superficial, and is often described as throbbing or burning. Pain intensity tends to increase during the day and worsen at night. Patients may experience allodynia, weight loss, chronic fatigue, depression, anxiety, and sleep disturbances.

Question 72

What are some risk factors for developing PHN?

Answer 72

Risk factors include older age, female sex, more intense acute pain, severe rash within three days of herpes zoster onset, sensory dysfunctions (e.g., increased tactile thresholds), and greater T-lymphocyte response in the acute phase.

Question 73

What are some risk factors for developing PHN?

Answer 73

Risk factors include older age, female sex, more intense acute pain, severe rash within three days of herpes zoster onset, sensory dysfunctions (e.g., increased tactile thresholds), and greater T-lymphocyte response in the acute phase.

Question 74

How does the risk of PHN change with age?

Answer 74

PHN is rare in individuals under 50 years old, but its incidence rises sharply after age 60. Older patients are more likely to develop PHN, particularly those with severe initial symptoms.

Question 75

What are the three types of PHN based on pain pathophysiology?

Answer 75

PHN can be divided into: Irritable nociceptors - due to abnormally functioning afferent neurons, causing spontaneous burning pain, allodynia, and reduced thermal threshold. Deafferentation-type pain with allodynia - characterized by profound sensory loss and mechanical allodynia. Deafferentation-type pain without allodynia - caused by CNS sensitization with complete loss of afferent input and intrinsic central changes.

Question 76

How can childhood vaccination prevent PHN?

Answer 76

Childhood vaccination against varicella (chickenpox) is the best preventative measure for PHN. Vaccination reduces the risk of herpes zoster reactivation and subsequent PHN development.

Question 77

What treatments are effective for PHN?

Answer 77

Treatments for PHN include antiviral medications during acute zoster, as well as antidepressants and anticonvulsants to manage chronic pain. Prompt treatment of herpes zoster reduces the risk of PHN.

Question 78

What is central neuropathic pain?

Answer 78

Central neuropathic pain results from injury to the central nervous system (CNS) and can arise from vascular, infectious, demyelinating, traumatic, or neoplastic disorders. It includes conditions like central poststroke pain (CPSP), multiple sclerosis (MS), and spinal cord injury (SCI).

Question 79

How is central neuropathic pain different from central sensitisation?

Answer 79

Central neuropathic pain is pain resulting directly from CNS injury, whereas central sensitization refers to increased excitability of neurons in the CNS, which can occur in any chronic pain condition.

Question 80

What are the characteristics of central neuropathic pain?

Answer 80

Central neuropathic pain can be continuous, paroxysmal, or evoked by stimuli like touch or temperature. It can be deep, superficial, or both, and is usually moderate to severe in intensity. Pain occurs in the body region affected by the CNS lesion.

Question 81

What are common causes of central neuropathic pain?

Answer 81

Common causes include stroke (central poststroke pain), spinal cord injury (SCI), and multiple sclerosis (MS). Thalamic and lateral medullary strokes are particularly likely to cause central neuropathic pain.

Question 82

What is central poststroke pain (CPSP)?

Answer 82

CPSP is a form of central neuropathic pain that occurs after a stroke, particularly in thalamic and lateral medullary strokes and affects the body region impacted by the stroke

Question 83

What are the main causes of spinal cord injury (SCI) leading to central neuropathic pain?

Answer 83

SCI most commonly affects young adults, with causes including motor vehicle accidents, falls, violence, and sports injuries. It results in burning, steady, dysesthetic pain that often includes phantom sensations below the level of injury.

Question 84

What is syringomyelia and how does it relate to SCI pain?

Answer 84

Syringomyelia is a condition where fluid-filled cysts compress the spinal cord, damaging nerves and tracts. It is a cause of central neuropathic pain in patients with spinal cord injury.

Question 85

What is the relationship between multiple sclerosis (MS) and central neuropathic pain?

Answer 85

MS is an autoimmune disorder causing demyelinating plaques in the brain and spinal cord. Central neuropathic pain affects 12-28% of MS patients, usually occurring more than a year after neurological symptoms develop.

Question 86

What are the underlying mechanisms of central neuropathic pain?

Answer 86

Central neuropathic pain stems from dysfunction in the spinal-thalamic-cortical pathways, with factors like denervation hypersensitivity, microglial activation, and disruption of descending inhibitory pathways contributing to pain generation.

Question 87

What is disinhibition and its role in central poststroke pain (CPSP)?

Answer 87

Disinhibition occurs when lesions in the thalamus lead to abnormal burst firing in the medial thalamus, acting as a central pain generator in CPSP.

Question 88

How is central neuropathic pain managed?

Answer 88

Treatment is challenging and often requires multimodal pharmacotherapy (e.g., pregabalin, antidepressants) and neuromodulation techniques like spinal cord stimulation, motor cortex stimulation, and deep brain stimulation for refractory pain.

Question 89

What is neuromodulation, and how is it used for central neuropathic pain?

Answer 89

Neuromodulation involves the use of electrical stimulation to modulate pain signaling. Techniques include spinal cord stimulation, motor cortex stimulation, and deep brain stimulation, targeting specific areas to interrupt pain signaling or enhance inhibitory pathways.

Question 90

Why can't spinal cord stimulation be used for CPSP?

Answer 90

Spinal cord stimulation is ineffective for CPSP because it targets the posterior sensory columns of the spinal cord, whereas CPSP originates from thalamic or supratentorial brain lesions.

Question 91

What is the difference between CPSP and SCI-related pain in terms of onset presentation

Answer 91

CPSP often has a delayed onset (weeks to months post-stroke), while SCI-related pain can be immediate and is usually associated with phantom sensations. CPSP affects the area impacted by the stroke, whereas SCI pain involves regions below the level of injury.

Question 92

What are the typical symptoms of central neuropathic pain following a spinal cord injury?

Answer 92

What are the typical symptoms of central neuropathic pain following a spinal cord injury?

Question 93

How do phantom sensations differ from phantom limb pain?

Answer 93

Phantom sensations are non-painful feelings of a missing limb or body part, while phantom limb pain involves painful sensations in an amputated limb, often described as burning, cramping, or shooting pai

Question 94

What role do microglia play in central neuropathic pain?

Answer 94

Microglial activation occurs in response to spinal cord injury, leading to increased activation of surviving spinothalamic tract neurons, contributing to central neuropathic pain.

Question 95

What are the key features of central neuropathic pain in MS patients

Answer 95

Central neuropathic pain in MS patients typically occurs in regions with spinothalamic tract sensory loss and is associated with accumulating levels of disability. It affects 12-28% of patients and often develops more than a year after initial neurological symptoms.

Question 96

What types of medications are commonly used for central neuropathic pain?

Answer 96

Common medications include anticonvulsants (e.g., pregabalin), antidepressants (e.g., tricyclic antidepressants), and NMDA receptor antagonists. Multimodal treatment is often necessary due to limited efficacy of individual agents.

Question 97

What is deep brain stimulation (DBS) and how does it help in central neuropathic pain?

Answer 97

DBS involves placing electrodes in specific brain areas to modulate pain signaling. It helps by disrupting pain pathways or enhancing descending inhibitory pathways, providing relief for refractory central neuropathic pain.

Question 98

How does neuromodulation differ from pharmacotherapy in treating central neuropathic pain?

Answer 98

Neuromodulation uses electrical stimulation to target specific pain pathways, while pharmacotherapy involves medications to alter neurotransmitter activity and reduce pain. Neuromodulation is often used when pharmacotherapy is ineffective

Question 99

What is the role of descending inhibitory pathways in central neuropathic pain?

Answer 99

Descending inhibitory pathways help regulate and reduce pain by suppressing nociceptive signaling. Dysfunction or disruption of these pathways can lead to increased pain perception in central neuropathic pain conditions.