Hyperesthesia – Causes, Symptoms, Treatment

Hyperesthesia is a condition that involves an abnormal increase in sensitivity to stimuli of the sense. Stimuli of the senses can include sound that one hears, foods that one tastes, textures that one feels, and so forth. Increased touch sensitivity is referred to as “tactile hyperesthesia”, and increased sound sensitivity is called “auditory hyperesthesia”. In the context of pain? hyperaesthesia can refer to an increase in sensitivity where there is both allodynia and hyperalgesia.^[rx]

Hyperesthesia occurs as a symptom of neuropathic pain? and can be present in any disease process that affects the somatosensory nervous system. Treatment involves treating underlying conditions and symptomatic support. A multidisciplinary approach that is able to provide timely diagnosis? and treatment, has the best outcomes. This activity outlines the evaluation and management of hyperesthesia and reviews the role of the interprofessional team in evaluating and treating patients with this condition.

The International Association for the Study of Pain? defines hyperesthesia as “increased sensitivity to stimulation, excluding the special senses,” which “may refer to various modes of cutaneous sensibility including touch and thermal sensation without pain, as well as to pain.” While hyperesthesia can be used to describe any increased sensitivity to a stimulus, it is commonly used to describe a painful sensation from a stimulus.

Hyperesthesia is a common symptom of neuropathic pain?. Neuropathic pain is defined by the International Association for the Study of Pain as “pain caused by a ulcer?. সহজ বাংলা: শরীরের অস্বাভাবিক দাগ, ক্ষত বা ফোলা অংশ।" data-rx-term="lesion" data-rx-definition="A lesion is an abnormal area of tissue such as a spot, wound, patch, lump, or ulcer. সহজ বাংলা: শরীরের অস্বাভাবিক দাগ, ক্ষত বা ফোলা অংশ।">lesion? or disease of the somatosensory system.” The neuropathic pain phenotype contains a spectrum of symptoms that can be roughly categorized into positive and negative symptoms. Hyperesthesia is a positive symptom of neuropathic pain. Positive symptoms are categorized as stimulus-dependent pain, stimulus-independent pain, and paresthesias.[rx] Neuropathic pain? affects about 7-8% of the general population.[rx][rx]

In this article, hyperesthesia will be defined as an increased cutaneous sensitivity manifesting as stimulus-dependent neuropathic pain?. The most common hyperesthesias are allodynia and hyperalgesia. Allodynia is a pain caused by a stimulus that usually does not elicit a painful response (i.e., pain on light touch). Hyperalgesia is an exaggerated pain response to a stimulus that usually causes pain (i.e., out of proportion pain from a pinprick). While most neuropathic pain symptoms are contained within the dermatomal distribution of the affected nerve, hyperesthesia has been known to extend beyond the affected nerve’s distribution. This can sometimes obscure the correct diagnosis? and lead to the inappropriate diagnosis of a psychosomatic disorder.[rx]

A detailed history and a thorough physical examination should be sufficient to identify the underlying etiology. Routine laboratories should be ordered as part of the workup. Special laboratory, diagnostic, and imaging tests may have to be ordered to make a definitive diagnosis? of the etiology. Treatable and reversible etiologies should be promptly treated. The mainstay of treatment is symptomatic relief via pharmacological, non-pharmacological, and interventional therapies. Symptoms are typically challenging to eliminate, and patients will most likely continue to experience persistent symptoms. A multidisciplinary team approach has been shown to provide the most effective and lasting results.

Causes of Hyperesthesia

Neuropathic pain? symptoms, including hyperesthesia, develop secondarily to a disease or a ulcer?. সহজ বাংলা: শরীরের অস্বাভাবিক দাগ, ক্ষত বা ফোলা অংশ।" data-rx-term="lesion" data-rx-definition="A lesion is an abnormal area of tissue such as a spot, wound, patch, lump, or ulcer. সহজ বাংলা: শরীরের অস্বাভাবিক দাগ, ক্ষত বা ফোলা অংশ।">lesion? of the nervous system that results in abnormal functioning of the somatosensory system. The etiology of hyperesthesia can be categorized anatomically or etiologically. Anatomically speaking, the source can be either central or peripheral.

Peripheral

• Systemic? disease: insulin? is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes? mellitus (DM), nutritional deficiency, thyroid? gland makes too little hormone. সহজ বাংলা: থাইরয়েড হরমোন কম।" data-rx-term="hypothyroidism" data-rx-definition="Hypothyroidism means the thyroid gland makes too little hormone. সহজ বাংলা: থাইরয়েড হরমোন কম।">hypothyroidism?, vasculitis, sarcoidosis, carcinoma/paraneoplastic, Guillain-Barre syndrome/acute? inflammatory demyelinating polyneuropathy, chronic? demyelinating inflammatory neuropathies, monoclonal gammopathy (amyloidosis, multiple myeloma, plasmacytoma, monoclonal gammopathy of undetermined significance), porphyria, Sjogren’s syndrome, and critical illness.
• Infectious: human immunodeficiency viruses (HIV), human T-cell lymphotropic virus, herpes simplex virus, varicella-zoster virus, Ebstein-Barr virus, West Nile virus, hepatitis? C virus, rabies virus, cytomegalovirus, diphtheria, Campylobacter jejuni, Mycobacterium tuberculosis, Mycobacterium leprae, Brucella spp., Clostridium botulinum, and Borrelia burgdorferi.[rx]
• Toxic:
  • Drugs: isoniazid, chemotherapeutics (vinca-alkaloids, taxanes, platinum compounds), statins, amiodarone, antimicrobials (isoniazid, linezolid, and metronidazole), and immunosuppressants (tumor necrosis factor inhibitors, leflunomide, and nucleoside analog reverse-transcriptase inhibitors).[rx]
  • Other toxins: ethanol and heavy metals
• Mechanical: trauma, compressive mononeuropathies, complex regional pain? syndrome type, post-amputation pain/phantom limb pain, trigeminal neuralgia, post-mastectomy pain syndrome, failed back surgery syndrome, and radiculopathies (nerve root compression)
• Hereditary: Charcot-Marie-Tooth disease and metachromatic leukodystrophy

Central

• Systemic? disease: B12 weakness?, numbness?, balance trouble, or coordination problems. সহজ বাংলা: স্পাইনাল কর্ডের সমস্যা।" data-rx-term="myelopathy" data-rx-definition="Myelopathy means spinal cord dysfunction, often causing weakness, numbness, balance trouble, or coordination problems. সহজ বাংলা: স্পাইনাল কর্ডের সমস্যা।">myelopathy?, multiple sclerosis?, spinal cord stroke?, brain stroke/central post-stroke pain? syndrome(CPSP), opioid-induced hyperalgesia, and infectious (Herpes simplex virus, myelitis, encephalitis)
• Mechanical: spinal cord injury, tumor compression (brain and spinal cord), syringomyelia, and weakness?, numbness?, balance trouble, or coordination problems. সহজ বাংলা: স্পাইনাল কর্ডের সমস্যা।" data-rx-term="myelopathy" data-rx-definition="Myelopathy means spinal cord dysfunction, often causing weakness, numbness, balance trouble, or coordination problems. সহজ বাংলা: স্পাইনাল কর্ডের সমস্যা।">myelopathy?[rx][rx][rx][rx]

Diagnosis of Hyperesthesia

History: A thorough history should be performed, as this should be sufficient to make a diagnosis of hyperesthesia.

• Past medical history (diabetes mellitis, stroke, fractures, irritable bowel syndrome)
• Psychiatric history (mood disorders)
• Medications (use of neurotoxic drugs) 
• Surgery
• Family history
• Sexual history
• Substance abuse (alcohol or opioid)
• Functional history: A functional history that examines the effect of the patient’s symptoms on their ability to function should be performed. It should focus on any impairments to the patient’s activities of daily living, instrumental activities of daily living, ambulatory status (use of assistive devices), work, or sleep.[rx]

• History of presenting illness: The examiner should gather a thorough description of the patient’s pain symptoms. The description of the patient’s symptoms should include all of the following components.

  • Location
  • Intensity (0-10 rating scale)
  • Quality (burning, cold, hot, or allodynia) Pain descriptors such as burning, tingling, or shooting are the most characteristic of neuropathic pain syndrome and have a high likelihood of being present along with hyperesthesia.[rx]
  • Onset (did the symptoms occur after an inciting event)
  • Temporal variation: At what time of the day is the pain worse? (neuropathic pain tends to be worse towards the end of the day) Has the pain progressively worsened over some time?
  • Radiation (does the pain have axial origin)
  • Positional variation (i.e., is the pain worse in the lower pack or the thigh)
  • Aggravating/alleviating factors
  • Attempted treatments (neuropathic pain symptoms are typically non-responsive to acetaminophen or nonsteroidal anti-inflammatory drugs)
  • Frequency
  • Associated symptoms (loss of range of motion, skin or hair changes, muscle spasms, muscle weakness, changes in sensation, redness, or swelling)

Physical exam: A complete neurological exam should be performed in addition to a general focused physical exam.

• Cranial nerve testing (CNS lesions may have cranial nerve involvement)
• Manual motor testing (weakness may be present in both peripheral and central etiologies, and any weakness should be differentiated as either real weakness or antalgic weakness)
• Deep tendon reflexes (may be brisk in central etiologies and diminished in peripheral etiologies)
• Sensory testing
  • Light touch (allodynia)
  • Pinprick (hyperalgesia)
  • Vibration and  proprioception
• Temperature (ice and hot packs for possible thermal allodynia)
• Straight leg test or slump test (radiculopathy)
• Tinel’s sign (peripheral nerve entrapment)
• Myofascial trigger points
• For complex regional pain syndrome (CRPS), a skin examination should be performed focusing on cutaneous temperature discrepancies, color changes, hidrosis, scars in a dermatomal distribution, and hair changes.

Evaluation

The first step should be to determine whether the etiology is peripheral or central. It is essential to accurately diagnose the cause of hyperesthesia to provide treatment of any treatable underlying cause.

Laboratory tests:

• Routine: Should be considered as part of a standard workup of peripheral hyperesthesia
  • Complete blood count
  • Comprehensive metabolic panel
  • Fasting blood glucose
  • Erythrocyte sedimentation rate
  • Thyroids stimulating hormone
  • Vitamine B12
• If indicated, based on clinical suspicion:
  • Hemoglobin A1c (HbA1c)
  • HIV antibodies
  • Liver panel
  • Lyme antibodies
  • Rapid plasma reagin (RPR), venereal disease research laboratory (VDRL)
  • Urinalysis
  • Urine protein electrophoresis
  • Serum protein electrophoresis
  • Angiotensin-converting enzyme levels
  • Antinuclear antibody (ANA) test
  • Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) test
  • Antineutrophil cytoplasmic antibodies (C-ANCA) test
• Tests for rare conditions
  • Paraneoplastic panel
  • Antimyelin associated glycoprotein
  • Antiganglioside antibodies
  • Salivary flow rate
  • Cerebrospinal fluid analysis
  • Genetic testing

Imaging: imaging is typically not needed to diagnose hyperesthesia, but it helps diagnose specific conditions.

• Computed tomographic scan and magnetic resonance imaging (nerve root compression, herniated disc, myelopathy, tumor in the brain or spinal cord)
• Triple phase bone scan (can be used to support a diagnosis of CRPS)[rx]

Special Tests:

• Electrodiagnostics: electromyography and nerve conduction studies (only tests large fibers)
• Punch skin biopsy (identifies small-fiber neuropathy)[rx]
• Diagnostic tests: Your doctor may recommend an electrodiagnostic test such as a nerve conduction study to measure the electrical activity of muscles and nerves. Diagnostic tests can help identify any nerve damage and the degree to which damage has occurred.
• Neurological evaluations: A neurological evaluation includes a physical examination and several painless tests to determine your neurological function. These tests help check muscle strength and your response to different sensory stimulations.

Treatment of Hyperesthesia

Treatment of hyperesthesia and other neuropathic pain symptoms is challenging but is best achieved by using a multidisciplinary team approach that can focus on treating underlying causes, administer pharmacotherapy, apply interventional therapy, address functional impairments, and provide mental health services if needed.[rx][rx] Realistic goals for hyperesthesia should be established early on. Any comorbidities such as mood disorders or sleep disturbances should be addressed promptly. Patients typically require close follow-up to monitor response to therapy and continued evaluation of the underlying cause.

For peripheral neuropathy, the most common treatable causes are diabetes mellitis, hypothyroidism, and nutritional deficiencies.[rx] Other causes of hyperesthesia, such as nerve root compression or peripheral nerve entrapment, may be initially treated conservatively with symptomatic pharmacotherapeutic support, physical therapy, lifestyle modifications, and minimally invasive procedures (i.e., epidural steroid injection or peripheral nerve injection). However, if there is worsening or stagnation of function, surgery may be required.

Pharmacological treatments can be used to treat both central and peripheral causes of hyperesthesia. Of the pharmacological options available, antidepressants and antiepileptic drugs are the most widely used.[rx] General guidelines for treatment are provided below; however, recommendations for the treatment of choice for specific etiologies are provided.

First-line drugs: These drugs have the most substantial evidence to support their treatment of neuropathic pain symptoms. This group contains two classes of antidepressants and one class of antiepileptic drugs.

• Antidepressants: all medications in this class have the added benefit of treating comorbid mood disorders.
  • TCAs: Amitryptiline, imipramine, and nortriptyline
    • Indications: painful diabetic neuropathy (PDN), postherpetic neuralgia (PHN), central poststroke pain (CPSP)
  • SNRIs: duloxetine and venlafaxine
    • Indications: PDN, post-traumatic neuropathic pain, CRPS, radiculopathy, and central pain
• Antiepileptic drugs:
  • Gabapentinoids: Gabapentin and pregabalin
    • Indications: PDN, PHN, central pain, posttraumatic neuropathic pain, CRPS, radiculopathy. Pregabalin has proven to be effective in the treatment of spinal cord injury central pain.[rx][rx]

Second-line treatments:

• Topicals
  • Lidocaine 5% patch
  • Capsaicin 8% patch: should ideally be applied by specially trained healthcare providers, as it requires pretreatment with topical lidocaine. May require postprocedural analgesics for 7-10 days. Relief may last up to 3 months.
    • Indications: PHN and HIV associated neuropathy

• Analgesic
  • Tramadol: Nonspecific analgesic, Mu-opioid receptor agonist but also blocks serotonin and norepinephrine reuptake.

Third-line treatments:

• Strong Opioids
  • Indications: Phantom pain, CRPS, central pain, PHN, and PDN
• Botulinum toxin-A
  • Indications: PHN

Not all patients will respond to monotherapy; in fact, 45% of individuals with neuropathic pain are on two or more medications for their pain. If a patient fails first-line monotherapy, they can be used in combination (i.e., gabapentinoid + TCA or SNRI).[rx]

Interventional Therapies:

• Epidural steroid injections: considered third-line therapy.
  • Indications: Radiculopathies[rx][rx]
• Sympathetic nerve block
  • Indications: CRPS patients who have failed other treatments.[rx]
• Neurostimulation: Fourth-line treatment[rx]
  • Spinal cord stimulation:
    • Indications: CRPS and failed back surgery syndrome (FBSS)[rx]
  • Motor cortex stimulation:
    • Indication: CPSP and facial pain
• Transcutaneous electrical nerve stimulation (TENS)

Some interventional treatments currently being practiced lack robust trials to be recommended by the guidelines. Some of the interventions that require continued research are radiofrequency denervation of the dorsal root ganglion, adhesiolysis for FBSS, TENS, spinal cord stimulation, and motor cortex stimulation.