Approach to Neuropathic Pain

Neuropathic pain is a common chief complaint encountered by neurologists and primary care providers. It is caused by disorders involving the somatosensory nervous system. The clinical evaluation of neuropathic pain is challenging and requires a multifaceted systematic approach with an emphasis on a thorough history and physical examination to identify characteristic signs and symptoms. Ancillary laboratory investigations, targeted imaging, and electrodiagnostic studies further help identify underlying etiologies to guide specific treatments. Management of neuropathic pain encompasses treating the underlying pathology as well as symptomatic control with nonpharmacological, pharmacological, and interventional therapies. Here, we present an approach to help evaluate patients with neuropathic pain.

Chondroitin Sulphate and Glucosamine Sulphate Synergistically Reduced DRG Proinflammatory Molecules and Improved Axonal Function in Sciatic Nerve Ligated Rats.

Neuropathic pain (NP) is a sickness of the somatosensory nervous system. It is linked to defective quality of life and often poorly managed. Due to the limited number of approved drugs, limited efficacy and side effects associated with them, drugs or drug combinations with great efficacy and very minimal or no side effects will be of great advantage in managing NP. This study aimed at investigating the synergistic antinociceptive effects of the combination of glucosamine sulphate (GS) (240mg/kg) and chondroitin sulphate (CS) (900mg/kg) in chronic constriction injury (CCI)-induced neuropathy in rat. Forty-two Wistar rats were randomly distributed into seven groups (n=6). Sciatic nerve was ligated with four loose ligatures to induce NP. Effects of drugs were examined on stimulus and non-stimulus evoked potentials, expression of dorsal root ganglia (DRG) pain modulators and structural architecture of DRG. Oral administration of GS and CS for 21 days reduced hyperalgesia, allodynia, sciatic nerve functional aberration and DRG pain modulators. Histopathology and immunohistochemistry revealed restoration of structural integrity of DRG. Our result showed that the combination of GS and CS produced antinociceptive effects by attenuating hyperalgesia, allodynia and downregulation of NP mediators. GS and CS additionally produced synergistic analgesic effect than its individual components.

Palmitoylethanolamide (PEA) in the treatment of neuropathic pain: a case study

Background: Neuropathic pain is a condition caused by a lesion or disease of the somatosensory nervous system. It may present as debilitating pain with a sensation of burning and electric-like symptoms and is often difficult to manage effectively. Although pharmacological medications are the first line of treatment, multidisciplinary teams are sometimes required to provide appropriate treatment to improve quality of life and overall wellbeing. Aim: The aim of this study is to present a case of post herpetic neuralgia relieved successfully by the compound palmitoylethanolamide (PEA) – a natural alternative to pharmacological pain relief. Methods: We present the case of a 67 year-old male with ongoing post-herpetic neuralgia, over a 3-year period, as a result of complications from shingles (herpes zoster). Previous studies on the relationship between PEA and neuropathy were reviewed, with an attempt to discuss the possible underlying mechanism of PEA on neuropathic pain. Results: PEA demonstrated effective pain relief within 48 hours at an administered daily dose of 900 mg (10 mg/kg). Conclusions: PEA may offer a valid nutraceutical treatment for practitioners.

Painful neuropathy: comparative observational analysis of safety profile of pregabalin and amitriptyline

Background: Chronic neuropathic pain, caused by a lesion or disease of the somatosensory nervous system is a common debilitating condition in clinical practice. Pregabalin and Amitriptyline are most commonly used drugs for its management. The aim of the study was to study the safety of Pregabalin and Amitriptyline in chronic neuropathic pain.Methods: Prospective observational study at Department of Medicine and Orthopaedics at All India Institute of Medical Sciences, Rishikesh. Newly diagnosed patients of neuropathic pain who were prescribed either Pregabalin or Amitriptyline were included in the study. Patients were followed up telephonically or during routine visits for a period of 3 months after initiation of any of these drugs. Appropriate measures of central tendency were used to describe demographic and clinical parameters and Correlation test was used between different variables and occurrence of adverse drug reactions.Results: 317 patients were prescribed these drugs. A total of 276 ADRs were observed (128 with Pregabalin and 148 with Amitriptyline). Central nervous system symptoms like sedation and dizziness were most commonly present in both the groups. Diabetes mellitus (47.1%) was most common etiology for neuropathic pain. Causality assessment showed probable association with Amitriptyline (n=140) and Pregabalin (n=118). Majority of ADRs with Amitriptyline group (49.32%) were moderate in severity whereas it was mild with Pregabalin (59.7%). A weak positive correlation (R=0.273) was seen with number of ADRs occurrence and total drug exposure in patients taking Pregabalin whereas a weak negative correlation (R=-0.623) was seen in Amitriptyline treated group.Conclusions: Safety profile of Pregabalin was better than Amitriptyline in the present study. The study findings must be replicated in larger patient population and for a prolonged duration for better understanding of the pattern of adverse drug reactions.

Neuropathic pain in children

Lesions or disease of the somatosensory nervous system can produce neuropathic pain (NP). Typical features include spontaneous or paroxysmal pain, often described as burning, shooting, like electric shocks, or pins and needles. NP does occur in childhood, but age at the time of injury may influence the risk of NP following traumatic nerve injuries. Whilst conditions commonly associated with NP in adults may be less common in childhood (e.g., trigeminal neuralgia), other conditions (e.g., Fabry’s disease and erythromelalgia), may present with pain in childhood and present a diagnostic challenge for paediatric practitioners.

Neural Plasticity in the Brain during Neuropathic Pain

Neuropathic pain is an intractable chronic pain, caused by damage to the somatosensory nervous system. To date, treatment for neuropathic pain has limited effects. For the development of efficient therapeutic methods, it is essential to fully understand the pathological mechanisms of neuropathic pain. Besides abnormal sensitization in the periphery and spinal cord, accumulating evidence suggests that neural plasticity in the brain is also critical for the development and maintenance of this pain. Recent technological advances in the measurement and manipulation of neuronal activity allow us to understand maladaptive plastic changes in the brain during neuropathic pain more precisely and modulate brain activity to reverse pain states at the preclinical and clinical levels. In this review paper, we discuss the current understanding of pathological neural plasticity in the four pain-related brain areas: the primary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray, and the basal ganglia. We also discuss potential treatments for neuropathic pain based on the modulation of neural plasticity in these brain areas.

Rationalized Approach for The Treatment of Neuropathic Pain

Injury to the nerves causes alteration in normal neurobiological sequences lead to disease of somatosensory nervous system called as neuropathic pain (NP). It affects both central as well as peripheral nervous system. It is a chronic painful condition occurs due to various diseases like HIV, diabetes, lesions, infection, trauma, and metabolic insults. NP affects 7-10% of global population, hence subsequently is a major concern. Pharmacotherapy for NP remains a major clinical challenge due to its complex pathophysiology. Current treatments like Analgesics, anticonvulsants, non-steroidal anti-inflammatory drugs, tri-cyclic antidepressants, sodium channel blocker and opioid agonist administrated individually to patients of NP are providing only meager and partial relief. Furthermore, these drugs have limited efficacy as well as adverse effects. Hence instead of monotherapy, pathophysiology of NP suggests that administering multiple drugs (polypharmacy) show quick and sufficient effect in the treatment of NP. Recent updates indicate that combination of Morphine and gabapentin, Pregabalin and duloxetine, Gabapentin and nortriptyline, Amitriptyline and ketamine (topical), Doxepin and capsaicin (topical), Glyceryl trinitrate (topical) and valproate are also a good choice for the treatment of NP. Several clinical trials also established that combination pharmacotherapy showed greater efficacy than monotherapy in treating NP. Physicians, scientists working in the area of NP are not only looking for its treatment but also in resolving the issues of co-morbidities associated with it. Hence the present review focuses on rationalized approach of combination therapy for the treatment of various aspects of NP.

Clinical Scale for Neuropathic Pain

Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is underdiagnosed and difficult to treat. Questionnaires based on self-reported symptoms have improved diagnosis and management of neuropathic pain. Visual analog scale and numeric rating scale are most well-known unidimensional pain questionnaires. Multidimensional questionnaire or specialized questionnaire for neuropathic pain are more useful to diagnose neuropathic pain. Screening questionnaires help to identify neuropathic pain easily, and assessment questionnaires make it possible to create phenotypic profiles of neuropathic pain and determine an efficacy of management.

Increased expression of Netrin-4 is associated with allodynia in a trigeminal neuropathic pain model rats by infraorbital nerve injury

Neuropathic pain refers to pain caused by lesions or diseases of the somatosensory nervous system that is characteristically different from nociceptive pain. Moreover, neuropathic pain occurs in the maxillofacial region due to various factors and is treated using tricyclic antidepressants and nerve block therapy; however, some cases do not fully recover. Netrin is a secreted protein crucially involved in neural circuit formation during development, including cell migration, cell death, neurite formation, and synapse formation. Recent studies show Netrin-4 expressed in the dorsal horn of the spinal cord is associated with chronic pain. Here we found involvement of Netrin-4 in neuropathic pain in the maxillofacial region. Netrin-4, along with one of its receptors, Unc5B, are expressed in the caudal subnucleus of the trigeminal spinal tract nucleus. Inhibition of its binding by anti-Netrin-4 antibodies not only shows a behavioral analgesic effect but also neuronal activity suppression. There was increased Netrin-4 expression at 14 days after infraorbital nerve injury. Our findings suggest that Netrin-4 induced by peripheral nerve injury causes neuropathic pain via Unc5B.

Role of Peripheral Immune Cells for Development and Recovery of Chronic Pain

Chronic neuropathic pain (CNP) is caused by a lesion or disease of the somatosensory nervous system. It affects ~8% of the general population and negatively impacts a person's level of functioning and quality of life. Its resistance to available pain therapies makes CNP a major unmet medical need. Immune cells have been shown to play a role for development, maintenance and recovery of CNP and therefore are attractive targets for novel pain therapies. In particular, in neuropathic mice and humans, microglia are activated in the dorsal horn and peripheral immune cells infiltrate the nervous system to promote chronic neuroinflammation and contribute to the initiation and progression of CNP. Importantly, immunity not only controls pain development and maintenance, but is also essential for pain resolution. In particular, regulatory T cells, a subpopulation of T lymphocytes with immune regulatory function, and macrophages were shown to be important contributors to pain recovery. In this review we summarize the interactions of the peripheral immune system with the nervous system and outline their contribution to the development and recovery of pain.