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Neuropathic pain

Neuropathic pain ( NP ) develops as a result of lesions or disease affecting the somatosensory nervous system either in the periphery or centrally


NEUROPATHIC PAIN –Disease process leads to a dysfunctional and abnormal 
somatosensory system


Nociceptive -Noxious perception from cellular damage Also called inflammatory Proportionate to magnitude of tissue damage →release of inflammatory mediators nociceptive pain can be somatic , visceral or referred Example of nociceptive pain is arthritis ie pain due to inflammatory mediators which are otherwise processed by a normal somatosensory system.


How common -Chronic pain is a common and frustrating problem which affects from 25 % to 65 % of the adult US population & WHO estimates that 22 % of the world’s primary care patients have chronic debilitating pain making chronic pain a problem which should be addressed by all health care professionals In the UK it is estimated that 1/3rd to 1/2 of the population suffer with chronic pain The estimation of neuropathic pain prevalence varies based on study centers and methodology used – these have been mostly gathered from studies in specialized cohorts as people with LBP , diabetes , MS , nerve entrapment syndrome Neuropathic pain appears to be common Several questionnaires as DN4 , S-LANSS can be used to asses neuropathic pains -studies using these questionnaires report a range of prevalence as between 3.3 % to 17.9 % Other studies quote that neuropathic pain affects 7% to 10 % of the general population


What happens Neuropathic pain encompasses a broad range of conditions which can be broadly divided as
- peripheral or central
- degenerative , traumatic , infectious , metabolic , toxic , autoimmune , chemotherapy induced peripheral neuropathies
- continuous or intermittent

 Neuropathic pain is thought to happen following nerve injury – injured neurons suffer changes along nocioceptive and descending modulatory pathways in CNS Various mechanisms have been proposed which include
- aberrant ectopic activity in nociceptive nerves
- involvement of a myriad of neurotransmitters ( development & maintenance )
- imbalances between excitatory and inhibitory signaling
- peripheral and central sensitization
- pathological activation of microglia
- alterations in ion channels and variability in the way pain messages are modulated in the CNS Several spinal cord conditions can cause neuropathic pain as spinal cord injury , syringomyelia , demyelinating diseases as multiple sclerosis , transverse myelitis , neuromyelitis optic.


Why is it important -Often difficult to treat with poor outcomes – recognised as one of the most difficult pain syndromes to manage NP can have multiple etiologies and presentations A study in Germany showed that 37 % of people with chronic LBP presenting in primary care had predominantly NP In the UK 26 % of diabetics were suffering with peripheral NP QoL is impaired as patients experience pain and in addition neuropathic pain is associated with depression , disordered sleep and impairment in physical function NP interferes with work , relationship and hobbies NP is more severe and associated with worse health in every measured dimension compared to non neuropathic pain Associated with increased drug prescriptions and use of healthcare services Treatment is mostly by trial and error as specific neuropathic pain mechanisms in a given patient cannot be identified to select a specific drug most likely to be effective Decreased productivity and lost work time – ie sig societal cost As population ages NP will present a rising health burden in future.


Suspecting neuropathic pain-It is not always easy but important to distinguish between neuropathic and nocioceptive pain Currently there is no international consensus how NP should be assessed in primary care and also in specialist settings Once you have assessed the pain for e.g using the SOCRATES acronym the following points may be helpful in identifying & managing NP

No transduction-In NP there is no conversion of a nociceptive stimulus into an electrical impulse.


Description-Most patient describe ongoing or intermittent spontaneous pain as burning , pricking , squeezing , electric shocks , tingling , pins & needles , shooting pain Often worse end of the day.


Positive and negative symptoms -Positive symptoms reflect an abnormal level of excitability in the NS and include pain , paraesthesia , dysesthesiae and spasm Positive symptoms can be stimulus -independent ( ie spontaneous ) and stimulus- dependent ( ie evoked ) Stimulus evoked pain includes allodynia , hyperalgesia and these can often be seen to extend beyond dermatomal or nerve territory distributions Negative signs and symptoms can include numbness , weakness , loss of deep tendon reflexes ( reduced impulse conduction in the neural tissue )


Allodynia -pain due to a stimulus that would normally not 
provoke pain ( for e.g light stroking )


Hyperalgesia / Hyperesthesia -increase in perception of pain generated by a stimulus that causes pain is hyperalgesia increased sensitivity to stimulation is hyperaesthesia


Paraesthesia -perception of anomalous sensations comparable to needle bites , tingling , itching , reduced or even loss of sensation


Associated conditions -NP is often associated with poor , sleep , depression , anxiety and the impact of the condition on QoL


Previous treatment -poor response to conventional analgesia previously tried medications


Risk factors -Older age Manual occupation Female sex Being unable to work Living in a rural area or council rented accommodation Lower educational attainment Growing evidence of genetic factors Underlying conditions like diabetes.


Assessment-Diagnosis of NP is based on clinical judgement , relevant clinical history and neurological examination Examination – cranial nerves , motor function , tendon reflexes ,muscle tone , walking pattern and balance Sensory evaluation to check tactile sensitivity , painful sensitivity , thermal sensitivity , 128 Hz vibrations sensation Always compare the side affected to the same contralateral area ( when pain is U/L ) and if B/L comparison evaluation should be proximal and distal to pain Pain clinics – neurophysiology , electrophysiology


Leeds Assessment of Neuropathic Symptoms and Signs – 4 symptom items – pricking , tingling , pins & needles , electric shocks , hot or burning sensations & pain evoked by light touching 1 item related to skin appearance 2 clinical examination items


Douleur Neuropathique questions 7 symptom item – burning , painful cold , electric shocks , tingling , pins & needles , numbness & itching 3 clinical examination items


Neuropathic Pain Questionnaire 7 sensory descriptors 3 items related to provoking factors 2 items describing affect.


pain DETECT Pain Disability Index Depression and Anxiety Stress Test Hospital Anxiety and Depression Scale


Possible fracture -is there a h/o major trauma or minor trauma in an elderly person ( ? osteoporotic bones )


Possibility of tumour , infection or inflammation-Age < 20 or > 50 h/o cancer Constitutional symptoms as fever , chills , weight loss recent bacterial infection IV drug use Immunosuppression Pain worsening at night or when supine.


Possible significant neurological deficit -severe or progressive sensory alterations or weakness bladder or bowel dysfunction.


Attitudes and beliefs-that pain is harmful or severely disabling expectation that passive treatment rather than active participation will help no one believes that pain is real.


Emotions and behaviours -fear avoidance behaviour low mood and social withdrawal.


Other psychosocial factors -poor family relationship or h/o abusive relationship financial issues work related problems ongoing legal issues due to persistent pain condition


Non-pharmacological -Acupuncture , massage therapy and reflexology.


Pharmacological -Calcium channel acting modulators ( pregabalin , gabapentin ) , tricyclic AD’s , SNRI’s ( duloxetine , venlafaxine ) are often used first line drugs.


Interventional -Anaesthetic and steroid 
inj’s , nerve blocks , spinal cord stimulation.


Generally difficult to treat , a major factor impacting outcomes is the presence of comorbidities as poor sleep , depressed mood and anxiety Literature quotes use of a multi-disciplinary team as pain is subjective & it is important to validate a patients pain , address psychosocial comorbidities and have realistic targets Evidence based guidelines are available but high quality evidence-based recommendations are lacking It has been noted that it is the intensity of the NP rather than the cause that was most important in determining the extent of its health impact Several guidelines have.


 care Several guidelines mention MDT care as a key component of care Shown to be statistically significantly decrease pain & improve function , mood , catastrophizing and pain acceptance Early nonpharmacological and non-interventional therapies as psychology , physiotherapy , exercise and massage can be beneficial.


First line -offer a choice of amitriptyline , duloxetine , gabapentin or pregabalin if one drug is not effective or not tolerated try another and consider switching again consider tramadol if acute rescue therapy is needed ( consider short term as trial evidence only for use up to 4 weeks , evidence of long term benefit is lacking & high rates of withdrawal due to advese affects ) consider capsaicin cream for people with localised neuopathic pain


Spinal cord stimulation -for those who continue to experience neuropathic pain for atleast 6 months despite adequate / appropriate medical management specialised multidisciplinary team experienced in chronic pain management would assess people for treatment NICE has produced guidance for specilaised pain teams on other interventional therapies fo e.g percutaneous electrical nerve stimulation for refractory NP.


Referral -diagnostic uncertainty patient has severe pain or the pain interferes significantly with lifestyle , daily activities including sleep disturbance or their underlying health condition has deteriorated any red flag is suspected


Special Interest Group on NP has proposed the following for peripheral NP first line Gabapentinoids , 
TCAs , SNRIs Second line -Lidocaine , Capsicin 
and Tramadol

Third line -Morphine , Oxycodone , botulinum toxin -A


Printable 2 page leaflet from Lancashire Medicines Management Group

Brain and Spine Foundation – What is neuropathic pain a good quick review with treatment options

National Institute of Neurological Disorders and Stroke – Peripheral Neuropathy Fact Sheet , a comprehensive explanation

British Acupuncture Society on Neuropathic pain and how acupuncture can help

Multiple Sclerosis Society on neuropathic pain – the invisible illness

American Chronic Pain Association – Neuropathic pain



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