Nevro Corp. (CA, USA), a manufacturer of medical devices for pain relief, has recently announced that it has received approval from the US FDA to commence a clinical trial of its Senza™ High-Frequency Spinal Cord Stimulation System for the treatment of chronic pain.
Chronic pain can be a highly debilitating condition and patients suffering with chronic pain can find that it negatively affects all aspects of their lives. The use of spinal cord stimulation involves the delivery of electrical pulses directly to the spinal cord, masking the pain signals being sent to the patient‘s brain. Spinal cord stimulation devices are implanted under the patient‘s skin, with small electrodes placed to the spinal column. While it has been demonstrated previously that this treatment method can reduce the pain felt by a patient, spinal cord stimulation can be associated with paresthesia, a tingling or numbing sensation experienced by patients.
The Nevro system is designed to act in a similar manner to existing technologies but to deliver the electrical pulses to the patient‘s spine at a greater rate. Data produced by earlier clinical trials conducted with the device, which has already received the CE mark of regulatory approval in Europe, suggest that the device may be successful in treating chronic pain that has not responded to spinal stimulation previously, and that it may have a reduced occurance of paresthesia compared with other similar devices. In the European study, patients mentioned a median reduction in back pain at 6 months (measured using a visual analog scale) of 78% while using the device and a median reduction of 83% in leg pain. The reduction in pain was found to continue to 1 year and patients did not experience paresthesia.
Leonardo Kapural, medical director of Wake Forest University Health Sciences, Chronic Pain Center in Winston-Salem (NC, USA), is acting as the lead investigator of Nevro‘s SENZA-RCT study and commented, “There is a real, unmet need for additional treatment options for chronic pain patients … Early studies suggest that high-frequency spinal cord stimulation may expand the group of patients treatable with spinal cord stimulation therapy while eliminating paresthesia, a highly unpleasant side effect of current systems. If these benefits are confirmed in the SENZA-RCT study, Nevro‘s high-frequency spinal cord stimulation system could represent an important breakthrough in the management of chronic pain.”
The SENZA-RCT study is a multicenter study that aims to enroll 300 patients and is a prospective, randomized, controlled trial. A unique aspect of the study is that it will include spinal cord stimulation in both trial arms. Nevro‘s high-frequency device will be compared with conventional low-frequency spinal cord stimulation.
– Written by Sean Fitzpatrick
Source: Nevro Corp: http://nevro.com/corporate/news
According to results of research conducted by G Lorimer Moseley (University of South Australia, Australia) and colleagues, the brain can be trained to reduce pain; a possible approach for the treatment of both phantom limb pain and complex regional pain syndrome.
Moseley, a clinical neurosciences professor at University of South Australia and Neuroscience Research Australia as well as the head of the Body in Mind research group explained his rationale to the audience attending the American Pain Society‘s Annual Scientific Meeting. He explained to the audience how the brain stores maps of the body that have been integrated with neurological systems. This leads to regulation, protection and surveillance which protects the body both psychologically and physically. According to Moseley, the very cortical maps which manage perception, sensation and movement are disrupted in people who experience chronic pain, “We‘re learning that chronic pain is associated with disruption of brain maps of the body and of the space around the body.” The mounting evidence comes mainly from phantom limb pain and complex regional pain syndrome sufferers but data collected from those with chronic back pain also exists.
Moseley‘s research areas consist of the role of both the brain and mind in chronic and complex pain disorders. The Body in Mind research group explores how the brain and the brain‘s representation of the body changes when pain persists, as well as how the mind can influence the physiological regulation of the body. The team, helped by patients, clinicians and scientists also see how the changes that the brain and mind undergo can be normalized via treatment. Mosley also commented on the fact that in some cases the body is not harmed but the brain causes a pain response as it mistakenly misinterprets a harmless stimulus as a harmful one; “We want to gradually train the brain to stop trying to protect body tissue that doesn‘t need protecting.”
In some cases of painful trauma the brain can undergo a process known as neuroplasticity whereby the brain rewires itself. Unfortunately in these instances the signaling pathways indicating damage do not turn off even after recovery from the trauma. This leads to chronic pain. Moseley believes that the brain can be reverted back to normality; “The brain is the focal point of the pain experience, but the plasticity phenomena can be harnessed to help alleviate pain.”
The very same brain maps that have been disrupted and continue to support the chronic pain status can themselves be targets for treatment. One such treatment approach named by Moseley is graded motor imagery. This is where visual images are used after prolonged painful stimuli to help alter the brain‘s perceptions of the body. Moseley explains how in conditions such as phantom limb pain, cortical maps still continue to include the limb that has since been severed and where pain continues to be produced even after there is no stimulus from the region. Studies have shown that using graded motor imagery has produced encouraging results in both phantom limb pain and complex regional pain syndrome and as Moseley explains, “Our work shows that the complex neural connections in the brain not only are associated with chronic pain, they can be reconnected or manipulated through therapy that alters brain perceptions and produce pain relief.”
– Written by Priti Nagda
Source: American Pain Society: www.ampainsoc.org/press/2012/training-brain.html
Researchers from Yale University and the West Haven Veterans Affairs Medical Center (CT, USA) have identified a potential source of neuropathic pain in diabetic patients. Nearly half of all diabetic patients are known to suffer from neuropathic pain, thus representing a major public health problem. However, much still remains unknown about the cause of diabetic neuropathies.
“How diabetes leads to neuropathic pain is still a mystery,” explained Andrew Tan, an associate research scientist in neurology at the Yale School of Medicine and lead author of the study. “An interesting line of study is based on the idea that neuropathic pain is due to faulty ‘rewiring‘ of pain circuitry.”
Previous work in the area has demonstrated the existence of a structure–function link between maladaptive dendritic spine plasticity and pain in CNS and PNS injury models of pain. In the study published in the May issue of the Journal of Neuroscience, the authors investigated whether dendritic spine remodeling contributes to neuropathic pain in streptozotocin-induced diabetic rats. Electrophysical and behavioral signs, as well as spine morphology were analyzed.
“Here we reveal that these dendritic spines, first studied in memory circuit processing, also contribute to the sensation of pain in diabetes,” Tan enthused. The investigators found that abnormal dendritic spines were associated with the onset of maintenance of pain. In addition, they also observed that a drug which interferes with the function of these spines reduced pain in laboratory animals therefore indicating that targeting these abnormal spines may be a potential therapeutic strategy of the future.
The authors concluded in their study, “These results demonstrate that diabetes-induced maladaptive dendritic spine remodeling has a mechanistic role in neuropathic pain. Molecular pathways that control spine morphogenesis and plasticity may be promising future targets for treatment.”
– Written by Paolo Reveglia
Sources: Yale News: http://news.yale.edu/2012/05/15/yale-team-discovers-unexpected-source-diabetic-neuropathy-pain; Tan AM, Samad OA, Fischer TZ, Zhao P, Persson AK, Waxman SG. Maladaptive dendritic spine remodeling contributes to diabetic neuropathic pain. J. Neurosci. 32(20), 6795–6807 (2012).
Migraine was once thought of as a vascular disease however, more recent research into its genetics and biology has found that it is an inherited disorder characterized by physiological changes in the brain, and it is a neurological disease with systemic implications. It is known that if attacks occur at high frequency structural alterations can occur in the brain.
Triptans have been used for the treatment of migraine in order to constrict the cerebral blood vessels. In a recent presentation to the American Pain Society, David Dodick (Mayo Clinic, AZ, USA), has stressed the importance of preventative therapies for the treatment of migraine. Investigations into the underlying causes of migraine have shown that treatment should focus on controlling the risk factors which could prevent episodic migraine sufferers from becoming chronic pain sufferers, which can be a debilitating disease leading to a reduced quality of life.
Several risk factors for migraine are: overuse of medication such as opioids, barbiturates, analgesics and triptans, mood disorders such as depression, obesity, head trauma and excess caffeine intake. Patients with these underlying risk factors could be treated in the primary care setting if general practitioners were educated in this form of therapy. Dodick commented “doctors need to take the time to think about the treatment of migraine rather than just the treatment of the pain”. It has been found that people with obesity have a fivefold increase in the risk of migraine and those people with depression have three times the risk. It was reported that if these patients can be treated on an everyday basis with known treatments such as antidepressants and blood pressure lowering medications the risk of migraine could be halved. Currently, approximately 40% of migraine sufferers would be candidates for preventative treatments while only 10% of these patients are being treated in this way.
The American Academy of Neurology and the American Headache Society issue new guidelines in April 2012 detailing new guidelines to endorse the use of preventative treatments stating that patients should be treated based on coexisting and comorbid conditions.
– Written by Claire Attwood
Sources: American Pain Society Press Room: www.ampainsoc.org/press/2012/risk-factor-management.html
A study by scientists from the University of California, San Francisco (UCSF; CA, USA) have shown how a cell therapy has the potential to be used to not only subdue notoriously hard to manage persistent chronic pain, but perhaps even cure the conditions giving rise to them. The research was performed on murine models of neuropathic pain achieved by transplanting immature embryonic nerves (arising in the brain during development) and instead used these cells to make up for the deficit of specific neurons that normally function to attenuate pain signals.
Of the transplanted cells, a portion matured to form functioning neurons, forming synapses and integrating into the existing nerve signaling pathways alongside their neighboring neurons.
This led to an almost complete abolishment of the pain hypersensitivity affiliated with nerve injury. In addition, there seemed to be no evidence of movement disturbances – common side effects of the favored conventional drug treatment route. Allan Basbaum, who chairs the Department of Anatomy at UCSF, and senior author of the study, commented on “the possibility of potential treatments that might eliminate the source of neuropathic pain, and that may be much more effective than drugs that aim only to treat symptomatically the pain from chronic, painful conditions.”
In some instances pain after trauma continue after healing leading to chronic pain. In neuropathic pain, the loss of specific inhibitory neurons leads to states of hyperexcitability so much so, that commonly, chronic pain can be induced by seemingly benign stimuli such as light touch, causing these to be perceived in a painful manner. Chronic pain becomes a debilitating condition, which some sufferers experience for many years.
The inhibitory neurons that have undergone damage within the spinal cord cannot release and transmit their normal mode of inhibition via the neurotransmitter GABA.
Currently gabapentin, an anticonvulsant used to treat epilepsy is the mainstay treatment for neuropathic pain. Although it does not completely mimic GABA it can compensate for the loss of inhibition normally provided by GABA. Unfortunately, according to Basbaum, it provides relief to only approximately 30% of sufferers.
Basbaum‘s colleagues at UCSF were already experimenting with transplanting immature neurons to produce GABA in murine models for the prevention of epileptic seizures and also Parkinson‘s – like disease. In these experiments, the transplanted cells (originating from the medial ganglionic eminence) within the forebrain were transplanted into the mouse brain.
Basbaum extrapolated this research and tried transplanting the immature cells into the spinal cord to try and combat neuropathic pain in order to compensate for the loss of GABA-driven inhibition. Such cells do not normally survive outside their natural environment with Alarez-Buylla observing that “one of the amazing properties of these cells from the medial ganglionic eminence is their unprecedented migratory capacity, to become functionally integrated with other cells.”
The next step for the UCSF research team will be to graft fetal human cells from either the medial ganglional eminence or human embryonic stem cells into rodent models to see whether human cells have the same capabilities or potential to relieve neuropathic pain.
– Written by Priti Nagda
Sources: UCSF News Center: www.ucsf.edu/news/2012/05/12055/chronic-pain-relieved-cell-transplantation-lab-study; Bráz JM, Sharif-Naeini R, Vogt D et al. Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain. Neuron 74(4), 663–675 (2012).