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3 INNOSC Theranostics and Pharmacological Sciences, 2022, Vol. 5, No. 2
2. Etiology
NP is associated with various medical conditions,
the causes of which vary considerably. Metabolic
(hypothyroidism), compressive (carpal tunnel
syndrome), infectious (huma immunodeficiency
virus, HIV), toxic (alcohol), traumatic (spinal cord
injury), and ischemic (diabetes) processes are all
causal factors of NP [19]. Multiple NP mechanisms
may be linked to a single medical issue. In
postherpetic neuralgia, viral, inflammatory, and
ischemic processes have been discovered.
Understanding the fundamental causes of NP may
lead to advancements in classification, diagnosis,
and treatment [20].
3. Classification of NP
Pain can be classified into neuropathic (pain
caused by damage to the nervous system) and
nociceptive (pain caused by stimulation of
peripheral nociceptors in the skin, joints, and
muscles). The primary distinction between NP
and nociceptive is that NP is characterized by a
lack of constant nociceptive input. Peripheral and
central NP is the two categories into which NP is
categorized [21]. A lesion or dysfunction causes
peripheral NP in the PNS, such as postherpetic
neuralgia, diabetic neuropathy, or causalgia.
Thalamic pain, post-stroke pain, and post-spinal
cord injury pain are examples of central NP that
are linked to CNS damage or dysfunction. In
addition, NP can either be induced by or unaltered
by stimuli. Hyperalgesia and allodynia brought on
by mechanical, thermal, or chemical stimulation
are what set stimulus-evoked pain apart. Chronic
or episodic, stimulus-independent (spontaneous)
pain is usually described as shooting, burning, or
stabbing [22].
4. Pathophysiology
There is currently no conclusive pathophysiology
for NP. It is impossible to predict the underlying
mechanisms based on a patient’s etiology of
the neuropathy, pain distribution, or symptoms.
There are several hypothesized mechanisms
of NP. NP can develop when there is injury or
pathological damage to the PNS or CNS [23]. To
summarize (Figure 2), the understanding of NP,
increased peripheral nerve firing, decreased CNS
©2022 AccScience Publishing
Dhokne et al.
inhibition, and altered CNS processes result in pain
amplification and propagation.
5. Pharmacological treatment for the
management of NP
The management of NP is quite challenging. Despite
taking the recommended medications for their
diseases, patients with NP will still generally suffer
from moderate to severe pain [23,24]. Therefore,
recommendations for the pharmaceutical therapy
of NP must be supported by data. Numerous
drugs have consistently demonstrated efficacy in
meta-analyses and randomized controlled clinical
studies, including antidepressants with serotonin
reuptake and norepinephrine inhibitors, Ca
2+
channel α2-δ2-ligands, opioid analgesics, and
topical analgesics such as lidocaine [25]. The mode
of action, information on dosage, and side effects
for different medication classes are summarized in
Table 1.
6. Preclinical animal models of NP
The high degree of variability in the etiology of NP,
which can be caused by conditions like diabetes
mellitus or anti-cancer chemotherapy, as well as
brain lesions, demyelinating diseases of the spinal
cord, and peripheral neuropathy, is a major concern
for research into and treatment of this condition [32].
Although the case histories of most NP patients do
not resemble those of preclinical studies, they do
allow for the investigation of disease processes,
and many clinically used treatments can reverse
the pain behaviors seen in these models [33]. The
majority of preclinical studies are carried out on
rodents and involve direct nerve injury to the sciatic
nerve. Animal models that mimic the etiology of
human diseases, such as diabetic neuropathy and
some chemotherapy medications, are available in
addition to surgical models [34,35]. However, due
to inefficiency or adverse effects, it has long been
difficult to effectively translate painkillers from
animal models to clinical studies [36,37]. Due to the
highly variable etiology of NP in humans compared
to the relatively constrained animal models, the
inbred (and thus genetically homogeneous) animal
subjects in comparison to the more genetically
diverse human population, and the difference in how
pain is assessed (i.e., most animal studies measure