Neuropathic pain can be caused by efferent activity (sympathetically maintained pain) or by afferent activity stoppage (deafferentation pain).
Neuropathic pain can be caused by peripheral nerve damage or malfunction. Here are several examples:
Mononeuropathies (involve a single nerve [ie, carpal tunnel syndrome, radiculopathy owing to a ruptured intervertebral disc]) (involve a single nerve [eg, carpal tunnel syndrome, radiculopathy due to a herniated intervertebral disk])
Plexopathies (involve several nerves inside a particular neural plexus; generally caused by trauma, inflammation, or nerve compression, as by a tumour) (involve multiple nerves within a particular neural plexus; typically caused by trauma, inflammation, or nerve compression, as by a tumor)
Polyneuropathies (involve several nerves, commonly across the body; often caused by various metabolic problems, paraproteinemias, toxic exposures [ie, alcohol, chemotherapy], inherited susceptibility, or, in rare cases, immune mediated pathways)
Neuropathic pain mechanisms are complex and involve changes
At the level of the peripheral nociceptor and nerve
Located in the dorsal root ganglion
Nociceptive routes and terminal structures in the central nervous system (CNS)
Injury causes inflammation as well as activation and over-representation of cation channels, particularly sodium channels, at the level of the peripheral nerve and nociceptor. These modifications lower the activation threshold and increase the sensitivity to unpleasant stimuli.
In chronic conditions, the peripheral nerve sends
Nociceptive ectopic impulses to the CNS on a constant basis. This continuous bombardment of peripheral nociceptive input causes changes in receptive nociceptors (central sensitization); they are primed, interpret pain from minor stimuli (including nonpainful stimuli [allodynia]) as significant pain, and interpret that pain as coming from a larger area than it actually does. If the peripheral nociceptive input is blocked, these alterations can be reversed, at least temporarily.
Central neuropathic pain syndromes (pain caused by malfunction of somatosensory pathways in the CNS) can originate from any CNS lesion, but they are most typically linked with a stroke, spinal cord injury, or a multiple sclerosis demyelinating plaque.
The pain must occur in the clinically affected area of the CNS lesion to be considered central neuropathic pain; however, it does not have to involve the entire affected area. Only when the spinothalamic tract (pinprick, temperature sensation) malfunctions does central neuropathic pain occur.
If pinprick and temperature sensations in the location of pain presumed to be central neuropathic pain are normal, another source of pain should be considered. Musculoskeletal discomfort is the most common source of pain in neurologically disabled patients (eg. shoulder pain related to arm paresis after a stroke or an upper extremity overuse syndrome in wheelchair-bound patients with a spinal cord injury).
Deafferentation pain is caused by a disruption in peripheral or central afferent neural activity. Here are several examples:
Central ache (pain after CNS injury)
Phantom limb discomfort (pain felt in the region of an amputated body part)
The mechanisms are uncertain, however they may entail central neuron sensitization, with reduced activation thresholds and receptive field enlargement.
Neuropathic pain disorders are sometimes connected with sympathetic nervous system overactivity. Although sympathetic overactivity does not cause neuropathic pain, it can add to its clinical characteristics and intensity.
The resulting pain is known as sympathetically sustained pain, and it is dependent on efferent sympathetic activity. Sympathetically sustained pain is a symptom of Complex Regional Pain Syndrome. Other types of neuropathic pain may also have a sympathetic component.
It is uncertain what causes sympathetic overactivity in some neuropathic pain states but not others. The mechanisms are most likely aberrant sympathetic-somatic nerve connections (ephapses), local inflammatory alterations, and spinal cord abnormalities.
Neuropathic Pain Symptoms and Signs
Dysesthesias (random or prompted searing pain, frequently with a lancinating component) are common, although pain can also be profound and agonising. Other sensations, such as hyperesthesia, hyperalgesia, allodynia (pain caused by a nonnoxious stimuli), and hyperpathia (an especially unpleasant, exaggerated pain reaction), may occur.
Patients may be unwilling to move the painful area of their body, leading in muscle atrophy, joint ankylosis, bone loss, and reduced mobility.
Because the CNS has been sensitised and altered, symptoms generally continue following resolution of the initial cause (assuming one was present).
Neuropathic Pain Diagnosis
When a nerve damage is known or suspected, the classic symptoms of neuropathic pain are present. The cause (for example, amputation, diabetes, or compression) may be obvious. If this is not the case, the diagnosis is frequently made based on a description of the symptoms; nevertheless, those descriptors (for example, scorching) are neither sensitive nor specific for neuropathic pain.
As a result, additional testing, such as a neurologic examination and electrophysiologic investigations, are necessary to confirm the diagnosis and identify the damaged nerve. Sympathetically sustained pain is pain that is alleviated by sympathetic nerve block.
Neuropathic Pain Treatment
Multimodal treatment (eg, physical methods, antidepressants, antiseizure drugs, psychotherapeutic methods, neuromodulation, sometimes surgery)
The treatment of neuropathic pain begins with confirming the right diagnosis and addressing curable causes (eg, herniated disk, carpal tunnel syndrome). Mobilization and physical therapy, in addition to medications, are required to desensitise areas of allodynia and prevent trophic alterations, disuse atrophy, and joint ankylosis.
Psychological issues must be taken into account from the beginning of treatment. Anxiety and depression must be properly treated. If the discomfort persists, neural blocking may be beneficial. When first-line medications fail to relieve dysfunction, patients may benefit from the holistic approach given by a pain clinic.
Neuromodulation (spinal cord or peripheral nerve stimulation) is especially useful in the treatment of neuropathic pain.
Several drug types are beneficial although complete alleviation is unlikely, and it is critical to set reasonable expectations. The goal of pharmacologic pain management is to make neuropathic pain less debilitating.
Opioid analgesics can provide some comfort, but they are often less effective than for acute nociceptive pain and carry the risk of dependence; side effects may limit appropriate analgesia.
Adjuvant analgesics, such as antidepressants and seizure medications
Most widely used to treat neuropathic pain, and randomised trial data supports their efficacy (1; see table Drugs for Neuropathic Pain).
Gabapentin is one of the most commonly utilised medications for this reason. For effective analgesia, the dose should be greater than 600 mg orally three times per day, and many individuals require a larger dose. The maximum recommended dosage is 1200 mg orally three times a day.
Pregabalin 100mg is identical to gabapentin but has more stable pharmacokinetics; two daily doses are equally effective as three daily doses and result in improved compliance. The target dose is at least 300 mg/day taken orally. Neuropathic pain disorders may necessitate up to 600 mg each day.
Even though the two medications have a similar basic mechanism of action. Some people who do not respond well to or tolerate gabapentin do respond to or tolerate pregabalin. Vice versa (binding to the alpha-2 delta ligand of the presynaptic calcium channel, which modulates nociceptive signaling).
The fundamental mechanism of action of tricyclic antidepressants (amitriptyline, nortriptyline, and desipramine) is the inhibition of serotonin and norepinephrine reuptake. Analgesic doses (75-150 mg orally once daily) are typically insufficient to relieve depression or anxiety.
Adverse anticholinergic and adrenergic effects frequently limit optimal dose. Secondary amine tricyclic antidepressants (nortriptyline and desipramine) have less side effects than tertiary amine tricyclic antidepressants (amitriptyline).
Pregalin 50mg that appears to be beneficial in the treatment of diabetic neuropathic pain, fibromyalgia, chronic musculoskeletal pain (including low back pain), and chemotherapy-induced neuropathy. Doses that are effective for depression, anxiety, and pain relief are similar.
The effects and mechanism of action of venlafaxine are similar to those of duloxetine.
For peripheral syndromes, topical medications and a patch containing lidocaine may be beneficial.
Other possibly successful therapies are as follows:
Spinal cord stimulation with an epidurally implanted electrode. For specific kinds of neuropathic pain (eg, chronic leg pain after spine surgery)
For certain persistent neuralgias, electrodes are placed along peripheral nerves and ganglia (peripheral nerve stimulation)
Except for some patients with complex regional pain syndrome, sympathetic blocking is usually unsuccessful.
Ablation or neural blockade (radiofrequency ablation, cryoablation, chemoneurolysis)
Electrical nerve stimulation through the skin (TENS)