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Chronic Pain
Emerging Treatments for Chronic Pain
a report by
Wahida Rahman, PhD
1
and Anthony H Dickenson, PhD
2
1. Post-doctoral Researcher; 2. Professor of Neuropharmacology, University College, London
Pain can be classified as acute (rapid-onset) or chronic (outlasting the efforts need to continue to boost the pharmaceutical profile of available
original insult by months/years). Chronic pain is different from acute agents by improving efficacy, tolerability, and pharmacokinetics, in
pain in that therapies that provide transient pain relief do not resolve addition to developing new chemical entities to manage pain refractory
the underlying pathological processes maintaining the pain; therefore, to current drugs. This article will focus on some of the molecular
it is not simply the duration of the pain that differentiates between mechanisms and targets that are currently attracting interest in chronic
acute and chronic pain, but also the inability of the body to heal itself. pain research.
Thus, damaged tissues and nerves can provide continued inputs into
the central nervous system that drive multiple changes at many levels of Excitatory Mechanisms—Blocking Aberrant Activity
the pain-signaling pathways. Since pain is not only a sensory response
but also an affective state, the pain produces a series of comorbidities Voltage-gated Sodium Channel Blockers
such as fatigue, anxiety, and depression. These interact to produce Sodium channel (Na
V
) blockers such as local anesthetics,
impaired quality of life in chronic pain patients. carbamazapine, etc. have been the mainstay of pain medicine for
decades, producing anesthesia and analgesia by preventing action
The signal interpreted as pain can be altered at many points along the potential propagation; however, blocking conduction is not their only
pain pathway, providing a multitude of strategic targets for rational role. Three of the nine isoforms of the human sodium channel family,
therapeutic intervention. However, despite the huge increase in our Na
V
1.7, 1.8, and 1.9, are expressed selectively in damage-sensing
understanding of the cellular and molecular mechanisms that initiate peripheral neurons.
1,2
Animal studies have demonstrated a role for these
and maintain maladaptive pain processing, chronic pain remains a huge channels in mechanosensation. Accordingly, mechanical hypersensitive
unmet clinical need. The pharmacopeia of available drugs is effective in behaviors akin to allodynia (painful experience to innocuous
some chronic pain patients, but not all of the time, due to disease stimulation, e.g. touch) and hyperalgesia (heightened pain experience
progression, low efficacy, and, more often, intolerable side effects. Thus, to painful stimuli) seen in chronic pain models are attenuated in tissue-
selective knock-out mice lacking these selective pain-related channels.
3
Wahida Rahman, PhD, is a post-doctoral researcher
working with Professors Anthony Dickenson and Stephen
Aberrant activity in damage-sensing peripheral fibers following
Hunt in the departments of Neuroscience, Pharmacology inflammation arises from the processes of peripheral sensitization,
and Physiology and Anatomy and Developmental Biology
whereas clustering of these channels at the site of injury and neuroma
respectively. Her research interests to date involve the
mechanisms of pain and she has published a number
after nerve injury is thought to be a major drive for the induction
of papers looking at the role of an anatomical pathway of disordered central processing.
3
The newly dense distribution along
originating in the spinal cord which directly targets the
the sensory neurone supports spontaneous firing of action potentials
brain and in turn loops back to the spinal cord–a circuit
designed to increase nociceptive transmission. Dr Rahman has a PhD and a Bsc in
along the neurone in the absence of peripheral stimuli. Additionally,
Pharmacology from University College, London. a concomitant upregulation of the embryonic Na
V
1.3 occurs,
w.rahman@ucl.ac.uk
whose biophysical properties and re-expression in adult neurones
after nerve injury have been associated with increased neuronal
Anthony Dickenson, PhD, is Professor of excitability and neuropathic pain.
4
However, a recent study has refuted
Neuropharmacology at University College, London. He
its role in nerve-injury or chronic inflammatory pain,
5
although its role
gained his PhD at the National Institute for Medical
Research, London, and has held posts in Paris, California
in central neuropathic pain could be considered on the basis of its
and Sweden. Professor Dickenson is an associate editor upregulation in thalamic nuclei.
6
Pre-clinical data point to a major role
for the journal Pain. He has given plenary lectures at the
for Na
V
1.7 in acute and inflammatory pain states.
7
Differential
World Congress on Pain, the American Pain Society, the
European Pain Congress, the Canadian Pain Society, the
mutations in the encoding gene, SCN9A, have been linked to the
Belgium Pain Society, ASEAPs, the Scandinavian Pain intense burning pain in erythermelalgia patients, a congenital absence
Society, the British Pain Society, the Thailand Pain Society, the Irish Pain Society, the
of pain perception, and reduced lidocaine effectiveness in some pain
Singapore Pain Society, the Australian Pain Society, the New Zealand Pain Society and
many other international and national meetings.
patients.
8,9
Understanding the genetic basis for altered nociceptive
profiles in chronic pain patients could lead to selective therapy on an
individual basis.
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