Tag: chronic pain

Categories : Neurology Pain ManagementTags :

A Step Closer to Effective Electrical Pain Blocking

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New research from the University of Connecticut has brought the drug-free technology of electrical anaesthesia for all chronic pain sufferers a step closer. 

Pain stimuli, or ‘nociceptive stimuli’ is picked up by nociceptors which send signals to the spinal cord, which passes it on to the brain where the perception of pain is manifested.

Bin Feng, associate professor in the Biomedical Engineering Department, led research which discovered how electrical stimulation of the dorsal root ganglia (DRG), sensory neural cell body clusters, can block nociceptive signal transmission to the spinal cord and prevent the brain from perceiving chronic pain signals. The findings are reported in PAIN.

Electrical devices to treat pain typically deliver electrical signals to the peripheral nervous system and spinal cord to block nociceptive signals from reaching the brain.

A major obstacle with these devices is that while some patients find them beneficial in relieving their chronic pain, others have little or no pain reduction. Despite incremental developments of neurostimulator technologies, there has not been much improvement in getting the devices to work for these patients.

“The trouble with this technology is that it can benefit a portion of patients very well, but for a larger portion of patients it has little benefit,” Prof Feng said.

One of the reasons is that such devices lag behind research into neural stimulation.

“We’re sitting on a huge pile of clinical data,” Prof Feng says. “But the science of neuromodulation remains understudied.”

Neurostimulators relieve pain according to a ‘gate control’ theory. Our bodies can detect both innocuous stimuli, like something brushing against the skin, and painful stimuli, through low- and high-threshold sensory neurons, respectively.

The spinal cord ‘gate’ can be shut by activating low-threshold sensory neurons, preventing painful nociceptive signals from high-threshold sensory neurons from crossing the spinal cord to the brain.

Neurostimulators reduce pain in patients by activating low-threshold sensory neurons with electrical pulses. This usually causes a non-painful tingling sensation in certain areas of the skin, or paresthaesia, masking the perception of pain.

Many patients receiving DRG stimulation treatment reported pain relief without the expected paraesthesia.

Seeking to understand this, Prof Feng’s lab discovered that electrical stimulation to the DRG can block transmission to the spinal cord at frequencies as low as 20 hertz. This is in contrast to previous research indicating that blocking requires kilohertz electrical stimulation.

“The cell bodies of sensory neurons form a T-junction with the peripheral and central axons in the DRG,” Feng says. “This T-junction appears to be the region that causes transmission block when DRG is stimulated.”

More remarkably, sensory nerve fibres with different characteristics are blocked by different electrical stimulation frequency ranges at the DRG, allowing the development of new neural stimulation protocols to enhance selective transmission blocking with different sensory fibre types.

“A-fibre nociceptors with large axon diameters are generally responsible for causing acute and sharp pain,” Prof Feng explained. “It is the long-lasting and dull-type pain that bothers the chronic pain patients mostIn a chronic pain condition, C-fibre nociceptors with small axon diameter and no myelin sheath play central role in the persistence of pain. Selectively blocking C-fibres while leaving A-fibres intact can be a promising strategy to target the cause of chronic pain.”

This provides evidence to place more electrodes for devices that target the DRG and surrounding neuronal tissues, letting doctors provide more precise neuromodulation.

“The next-generation neurostimulators will be more selective with fewer off-target effects,” Prof Feng said. “They should also be more intelligent by incorporating chemical and electrical sensory capabilities and ability to communicate bidirectionally to a cloud-based server.”

Prof Feng hopes that more people will be eventually able to achieve chronic pain relief with this technology. He is now working toward conducting clinical studies with his collaborators at UConn Health to test the efficacy of this method in humans.

Source: University of Connecticut

Categories : Pain ManagementTags :

Acupuncture Puts a Pin in Chronic Pelvic Pain

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A multicentre randomised trial showed that eight weeks of acupuncture sessions improved symptoms of moderate to severe chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to a greater extent than sham therapy. Treatment effects endured over 24 weeks follow up. The findings are published in Annals of Internal Medicine.

CP/CPPS manifests as discomfort or pain in the pelvic region for at least three of the previous six months with no infection, with possible involvement of lower urinary tract symptoms, psychological issues, and sexual dysfunction. Men with CP/CPPS may have a poor quality of life associated with the disorder, such as inflammation in the prostate, anxiety and stress, and dyssynergic voiding. Standard care involves antibiotics, a-blockers, and anti-inflammatories, but their effectiveness is limited and long-term use is associated with adverse events. Though promising as an alternative treatment, acupuncture lacks high quality evidence.

A total of 440 male participants were randomised to either 8 weeks of acupuncture or sham therapy to assess the long-term efficacy of acupuncture for improving symptoms of CP/CPPS. The treatment was considered effective if participants achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Between-group difference to be statistically significant at both time points for sustained efficacy. 

More participants in the acupuncture group reported marked or moderate improvements in symptoms at all assessment points compared to the sham control group. No significant difference was found in changes in International Index of Erectile Function 5 score at all assessment time points or in peak and average urinary flow rates at week 8. No serious adverse events were reported in either group.

According to the researchers, these findings show long-term efficacy of acupuncture and provide high-quality evidence for clinical practice and guideline recommendations.

Source: Medical Xpress

Categories : Pain ManagementTags :

Transcranial Focused Ultrasound for Chronic Pain Relief

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A rodent study has demonstrated the potential for transcranial focused ultrasound (tFUS) to relieve chronic pain and other symptoms.

Neuromodulation, or therapeutic stimulation of neurons with electrical energy. chemicals or potentially with acoustic waves, can amplify or dampen neuronal impulses in the brain or body to relieve symptoms such as pain or tremor.

Ultrasound is a promising non-invasive, non-surgical type of neuromodulation. It offers a temporary modulation that can be tuned for a desired effect. In this study, researchers have shown that it can be targeted at neurons with specific functions.

A team led by Bin He, PhD, professor of biomedical engineering at Carnegie Mellon University, and funded in part by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), has demonstrated the potential of a neuromodulation approach that uses low-intensity ultrasound energy, called transcranial focused ultrasound-;or tFUS. In a paper published in Nature Communications, the authors describe the use of tFUS in rodent experiments, demonstrating the non-invasive neuromodulation alternative.

Moria Bittmann, PhD, Director of the Program in Biorobotic Systems, National Institute of Biomedical Imaging and Bioengineering, said: “Transcranial focused ultrasound is a promising approach that could be used to treat forms of chronic pain, among other applications. In conditions where symptoms include debilitating pain, externally generated impulses of ultrasound at controlled frequencies and intensity could inhibit pain signals.”

The researchers designed an assembly that included an ultrasound transducer and a multi-electrode array, which records neuronal data. During experiments with anaesthetised rodents, the researchers sent acoustic pulses into the brain cortex, targeting specific neurons, while recording change in electrophysiological signals from different neuron types.

When neurons transmit signals, whether engaging the senses or controlling movement, the firing of that signal across the synapse is termed a spike. The researchers observed two types of neurons: excitatory and inhibitory neurons.

When using tFUS to emit repeated bursts of ultrasound stimulation directly at excitatory neurons, the researchers saw an elevated impulse rate, or spike. Inhibitory neurons subjected to the same tFUS energy however did not display a significant spike rate disturbance. This showed that the ultrasound signal can be transmitted through the skull to selectively activate specific neuron sub-populations, in effect targeting neurons with different functions.

“Our research addresses an unmet need to develop non-toxic, non-addictive, non-pharmacologic therapies for human use,” said Prof He. “We hope to further develop the tFUS approach with variation in ultrasound frequencies and to pursue insights into neuronal activity so that this technology has the optimal chance for benefiting brain health.”

There are many broad applications for this research. Prof He believes non-invasive tFUS neuromodulation could be used to facilitate treatment for many people suffering from pain, depression and addiction. “If we can localise and target areas of the brain using acoustic, ultrasound energy, I believe we can potentially treat a myriad of neurological and psychiatric diseases and conditions,” Prof He said.

Source: National Institute of Biomedical Imaging and Bioengineering

Categories : Gender Pain ManagementTags :

Unique Genetic Basis for Chronic Pain in Women Discovered

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A meta-analysis of UK genetic data has found a different genetic basis for chronic pain in women compared to men.

While the results are still preliminary, this is one of the largest genetic studies on chronic pain analysing by sexes.

“Our study highlights the importance of considering sex as a biological variable and showed subtle but interesting sex differences in the genetics of chronic pain,” said population geneticist Keira Johnston of the University of Glasgow in Scotland.

Chronic pain conditions are among the most prevalent, disabling, and expensive conditions in public health, and are frequently overlooked for research funding. With 100 million people in chronic pain in the US in 2016, overprescription of opioids for chronic pain has resulted in an epidemic of opioid misuse, with 66% of overdose cases being for opioids. Even very moderate opioid use carries the risk of addiction and abuse.

Even when studies are done, they often overlook underlying sex differences, and that’s a huge and detrimental oversight. Compared to men, women are far more likely to develop multiple chronic pain disorders, and yet historically, 80 percent of all pain studies have been conducted on male mice or male humans. This means we know very little about how and why females are suffering more and what treatments can help them best.

While there are probably multiple biological and psychosocial processes in this sex discrepancy, the current genome-wide study suggests there’s a genetic factor in the mix, too.

The researchers compared gene variants associated with chronic pain in 209 093 women and 178 556 men from the UK Biobank, and found 31 genes associated with chronic pain in women and 37 genes associated with chronic pain in men with barely any overlap. This might be due to the slightly smaller sample size of men but the results are nonetheless intriguing, the researchers maintained.

The vast majority of these genes were active in a cluster of nerves within the spinal cord, known as the dorsal root ganglion, which transmits messages from the body to the brain.
While several genes in the male-only or female-only list were linked with psychiatric disorders or immune function, only one, called DCC, was found in both lists.
DCC encodes for a receptor that binds with a protein crucial for the development of the nervous system, especially the dopaminergic system. The dopaminergic system is the ‘reward centre’ but also has been linked to pain.

DCC is also linked to depression, and DCC mutations appear in those with congenital mirror movement disorder, which results in movements on one side of the body being replicated on the other side.

It’s not how DCC is linked to chronic pain, but the researchers believe their results support several theories “of strong nervous system and immune involvement in chronic pain in both sexes”, which will, they hope, result in the development of better treatments.

Should chronic pain be more closely linked to immune function in women, immune-targeting drugs may have very different side-effects than in men. Opioids negatively impact immune function, indicating that they could in fact worsen the situation for women suffering chronic pain. However, more research is needed to strengthen these findings and understand their impacts.

“All of these lines of evidence, together, suggest putative central and peripheral neuronal roles for some of these genes, many of which have not been historically well studied in the field of chronic pain,” the authors concluded.

Source: Science Alert

Journal information: Johnston KJA, Ward J, Ray PR, Adams MJ, McIntosh AM, Smith BH, et al. (2021) Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genet 17(3): e1009428. doi.org/10.1371/journal.pgen.1009428