Researchers have discovered the recipe for painlessness

Researchers have discovered the recipe for painlessness

People born with a rare genetic mutation are unable to feel pain, but previous attempts to recreate this effect with drugs have had surprisingly little success. Using mice modified to carry the same mutation, UCL researchers funded by the MRC and Wellcome Trust have now discovered the recipe for painlessness.

‘Channels’ that allow messages to pass along nerve cell membranes are vital for electrical signalling in the nervous system. In 2006, it was shown that sodium channel Nav1.7 is particularly important for signalling in pain pathways and people born with non-functioning Nav1.7 do not feel pain. Drugs that block Nav1.7 have since been developed but they had disappointingly weak effects.

The new study, published in Nature Communications, reveals that mice and people who lack Nav1.7 also produce higher than normal levels of natural opioid peptides.

To examine if opioids were important for painlessness, the researchers gave naloxone, an opioid blocker, to mice lacking Nav1.7 and found that they became able to feel pain. They then gave naloxone to a 39-year-old woman with the rare mutation and she felt pain for the first time in her life.

“After a decade of rather disappointing drug trials, we now have confirmation that Nav1.7 really is a key element in human pain,” says senior author Professor John Wood (UCL Medicine). “The secret ingredient turned out to be good old-fashioned opioid peptides, and we have now filed a patent for combining low dose opioids with Nav1.7 blockers. This should replicate the painlessness experienced by people with rare mutations, and we have already successfully tested this approach in unmodified mice.”

Broad-spectrum sodium channel blockers are used as local anaesthetics, but they are not suitable for long-term pain management as they cause complete numbness and can have serious side-effects over time. By contrast, people born without working Nav1.7 still feel non-painful touch normally and the only known side-effect is the inability to smell.

Opioid painkillers such as morphine are highly effective at reducing pain, but long-term use can lead to dependence and tolerance. As the body becomes used to the drug it becomes less effective so higher doses are needed for the same effect, side effects become more severe, and eventually it stops working altogether.

“Used in combination with Nav1.7 blockers, the dose of opioid needed to prevent pain is very low,” explains Professor Wood. “People with non-functioning Nav1.7 produce low levels of opioids throughout their lives without developing tolerance or experiencing unpleasant side-effects. We hope to see our approach tested in human trials by 2017 and we can then start looking into drug combinations to help the millions of chronic pain patients around the world.”

The findings were made possible by the use of ‘transgenic’ mice, meaning they were modified to carry genetic material from another organism — in this case, the mutation that prevents humans from feeling pain. Precise physiological experiments showed that the nervous systems of the transgenic mice contained around twice the levels of naturally-produced opioids as unmodified mice from the same litter.

“Our results reaffirm the clinical relevance of transgenic mouse models for human diseases,” says Professor Wood. “Studying the mice showed us what was going on in the nervous system that led to painlessness and our findings were directly translatable to humans, as confirmed by the painless patient. Without the work in transgenic mice, none of this would have been possible and we still wouldn’t know how to replicate the effects to help people suffering from chronic pain.”

Story Source:

University College London. “Genetically modified mice reveal the secret to a painless life: Researchers have discovered the pharmaceutical recipe for painlessness.” ScienceDaily. ScienceDaily, 4 December 2015. <>

Journal Reference:

  1. Michael S. Minett, Vanessa Pereira, Shafaq Sikandar, Ayako Matsuyama, Stéphane Lolignier, Alexandros H. Kanellopoulos, Flavia Mancini, Gian D. Iannetti, Yury D. Bogdanov, Sonia Santana-Varela, Queensta Millet, Giorgios Baskozos, Raymond MacAllister, James J. Cox, Jing Zhao, John N. Wood. Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7Nature Communications, 2015; 6: 8967 DOI: 10.1038/ncomms9967


Latest Pain Research News

Latest Pain Research News

Scientific breakthroughs happen every day!  In an effort to help our patients stay up to speed on the most cutting edge treatment options available for them, our scientists monitor current research and publish weekly research updates.  The title of each article below is a link to the full study report.  If you’d like to make an appointment with Dr. Hanna to discuss your treatment options, please contact us.


Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli

F Hu, G Ding, Z Zhang, LA Gatto, S Hawgood… – Innate Immunity, 2015

UTI was induced as previously described, 30 with some modifications. In brief, mice were

anesthetized by ip injection with ketamine/xylazine (90 mg/kg ketamine and 10 mg/kg xylazine),

and were gently massaged and pushed down on the bladder to expel urine.

[PDF] Comparison of propofol and ketofol in minor gynecologic interventions

Y Işık, Z Kurdoğlu, U Göktaş, İ Katı, D Sözen – J Clin Exp Invest www. jceionline. org …, 2015

Propofol is administered as an infusion instead of in repeated doses, which prevents

dose-dependent respiratory and cardiovascular system depression and pro- vides controlled

sedation [1]. Ketamine is preferred for premedication, anesthesia induction and main- tenance

Anesthesia Complications of Pediatric Radiotherapy

V Verma, AB Beethe, M LeRiger, RR Kulkarni, M Zhang… – Practical Radiation …, 2015

While agents such as ketamine (complication rates approaching 23-24%) have been used

in the past, other agents such as propofol and volatile anesthetics have lower complication

rates due to improved drug side effect profiles (0.01-3.5%).

[HTML] Stress activates the nucleus incertus and modulates plasticity in the hippocampo-medial prefrontal cortical pathway

R Rajkumar, Y Wu, U Farooq, WH Tan, GS Dawe – Brain Research Bulletin, 2015

Ketamine (Parnell Manufacturing Pty Ltd; Alexandria, NSW, Australia), xylazine (Ilium Xylazil,

Troy Laboratories Pty Ltd; Glendenning, NSW, Australia), enrofloxacin (Baytril 5%, Bayer Health

Care; Seoul, Korea) and carprofen (Carprieve, Norbrook Laboratories (GB), Ltd

The role of glutamatergic, GABA-ergic, and cholinergic receptors in depression and antidepressant-like effect

K Pytka, A Dziubina, K Młyniec, A Dziedziczak… – Pharmacological Reports, 2015

Depression is one of the most common mental disorders and social issue worldwide. Although

there are many antidepressants available, the effectiveness of the th.

[HTML] Communicating with mismatch and tension: treatment provision experiences of primary care doctors treating patients with overactive bladder in Hong Kong

JY Siu – BMC Family Practice, 2015

[P6]. During the study period, the symptoms of OAB, particularly urinary frequency and

urinary incontinence, were identified by government antisubstance abuse public service

announcements as signs and consequences of ketamine abuse.

Hydrogen sulfide (H 2 S) attenuates uranium-induced acute nephrotoxicity through oxidative stress and inflammatory response via Nrf2-NF-κB pathways

J Zheng, T Zhao, Y Yuan, N Hu, X Tang – Chemico-Biological Interactions, 2015

sacrificed. After urine collection, rats were anesthetized by an ip injection of

ketamine-xylazine (50 mg/kg ketamine and 5 mg/kg xylazine), and blood samples

were obtained directly from the heart ventricle in anesthetized animals.

[PDF] General discussion and future perspectives

SA Bouwense, M de Vries, LT Schreuder, SS Olesen… – PDF hosted at the Radboud …, 2015

even if technically successful. If central nervous system pain processing is altered,

specific treatment targeting these changes should be instituted (eg gabapentinoids,

ketamine or tricyclic antidepressants). Suitable tools are

Propofol target-controlled infusion for sedated gastrointestinal endoscopy: A comparison of propofol alone versus propofol–fentanyl–midazolam

CD Hsu, JM Huang, YP Chuang, HY Wei, YC Su… – The Kaohsiung Journal of …, 2015

The currently used regimens include propofol, benzodiazepines (such as midazolam and

diazepam), opioids (such as fentanyl and remifentanil), ketamine, and de-dexmedetomidine

[3], [4], [5] and [6]. Among them propofol has become popular in developed countries, because

[PDF] A Critical Case of Closed Cervix Pyometra in a Bitch

JK Agrawal, A Saxena, P Kumar, A Patel – International Journal of Livestock Research, 2015

General anethesia was induced and maintained by a combination of ketamine hydrochloride @

5mg/kg and Xylazine @ 0.2mg/kg body weight intravenously following premedication with atropine

sulphate @ 0.04mg/kg body weight. Laparotomy was performed

Radiofrequency Ablation (RFA)

Treatment of Neuroendocrine Liver Metastases

HA Farley, RF Pommier – Surgical Oncology Clinics of North America, 2015

Treatment options: radiofrequency ablation. RFA is another technique used to treat

neuroendocrine metastases of the liver, but it has limitations. One can ablate a limited number

of lesions (generally up to 5), of limited size (generally <5 cm in diameter), provided they are

[PDF] Ablative Techniques in Advanced Pancreatic Cancer: Do They Affect The Quality of Life?–Review

D Dimitrov, H Feradova, D Gincheva, L Dall’Olio – JOP. J Pancreas (Online), 2015

Such ablative therapies are high-intensity focused ultrasound (HIFU), radiofrequency

ablation (RFA), irreversible electroporation (IRE), iodine-125, iodine-125–cryosurgery,

photodynamic therapy (PDT) and microwave ablation [8].

Minimally Invasive Techniques for Resection of Pancreatic Neuroendocrine Tumors

GGF Ranvier, D Shouhed, WB Inabnet – Surgical Oncology Clinics of North America, 2015

Please note that Internet Explorer version 8.x will not be supported as of January 1,

2016. Please refer to this blog post for more information. Close.

[HTML] Colorectal Liver Metastasis, Primary Gallbladder Carcinoma and Myelofibrosis Present Simultaneously in a Liver Resection Specimen

SA Gray, MH Raber, E Provoost, GJ Toes, JM Klaase – Case Reports in …, 2015

An elective operation was scheduled, and the surgeon performed a wedge resection of segments

5 and 7 of the liver, and a radiofrequency ablation was used to treat a lesion in segment 3.

Although the suspicion of gallbladder carcinoma at the time of surgery was low, the

Nontraumatic Cervical Spine for Primary Care Providers

CR Hemmer – The Journal for Nurse Practitioners, 2015

physical therapy, a home traction unit, transcutaneous electrical nerve stimulation, epidural steroid

injections, selective nerve root blocks (transforaminal injections), botulinum toxin type A injections,

medication management, radiofrequency ablation, and surgical correction.

Surgical Management of Adrenocortical Carcinoma: An Evidence-Based Approach

J Datta, RE Roses – Surgical Oncology Clinics of North America, 2015

Please note that Internet Explorer version 8.x will not be supported as of January 1,

2016. Please refer to this blog post for more information. Close.


S Narayan, R Sehra – US Patent 20,150,289,807, 2015

For instance, ablation success for atrial tachycardias (a ‘simple’ disorder) may be as low as 70%.

Thus, ablating the cause of a heart rhythm disorder can be challenging, and even experienced

practitioners may require hours to ablate certain ‘simple’ rhythm disorders


S Navalkissoor, G Gnanasegaran – Journal of Cancer & Allied Specialties, 2015

These include surgical debulking, chemotherapy, molecular targeted therapies (eg sunitinib

and everolimus), interferon, somatostatin analogues, local therapies (eg radiofrequency ablation

or embolisation) and peptide receptor radionuclide therapy (PRRT).

[PDF] Successful Radiofrequency Pulmonary Vein Isolation In A Patient With Pneumonectomy

F Kilicaslan, EE Gul, C Erol

Circumferential radiofrequency ablation of ipsilateral PVs was done (30-35 W, 17

mL/min) with irrigated catheter (Sprinklr, Medtronic, Minneapolis, USA) and both,

entrance and exit blocks were achieved after the ablation. Interestingly

[PDF] Ablation Is A Treatment Option Without Permanent Pacemaker Implantation For Bradycardia With Persistent Atrial Fibrillation

W Yamada, K Tanimoto, M Yamada, K Inagawa…

Page 5. Rotational Atriography Of Left Atrium – A Imaging Technique Used To Support Left Atrial

Radiofrequency Ablation: A Comparison Of Anatomical Data Of Left Atrium F. Lehar, Z. Starek,

J. Jez, J. Wolf, T. Kulik, A. Zbankova, M. Novak Department of Cardiology, ICRC/St.

Complex Regional Pain Syndrome (CRPS/RSD)

[PDF] Do insiders trade on mispricing after earnings announcements?

JP Fidrmuc, J Novák, H Contreras – 2015

Page 1. Do insiders trade on mispricing after earnings announcements? Jana P.

Fidrmuc∗ Warwick Business School Jirı Novák† Charles University Harold Contreras‡

Warwick Business School October 21, 2015 Abstract This

[PDF] A predictive framework for evaluating models of semantic organization in free recall

NW Morton, SM Polyn – Journal of Memory and Language, 2015

Research in free recall has demonstrated that semantic associations reliably influence the

organization of search through episodic memory. However, the specific.


GW Muller, H Man – US Patent 20,150,291,555, 2015

Examples of diseases or disorders include, but are not limited to, cancer, disorders associated

with angiogenesis, pain including, but not limited to, Complex Regional Pain Syndrome (“CRPS”),

Macular Degeneration (“MD”) and related syndromes, skin diseases, pulmonary

[PDF] Psychological distress and stressful life events in pediatric complex regional pain syndrome

MD Hannah Brehmer, MD Boris Zernikow

Complex regional pain syndrome (CRPS) is increasingly recog- nized as a serious pain

disorder in children and adolescents. Specifically, it is not known which factors precipitate

CRPS and which result from the ongoing painful disease.

[PDF] In the High Court of New Zealand Wellington Registry


Pain News 11 (1) 2013 pages 30-33. Safarfashandi Z, Munglani R, Safarfashandi L, Sadheura

J, Jenner C “The incidence of complex regional pain syndrome (CRPS) post trauma and the

possible role of tight plaster of Paris in the aetiology of CRPS“.

[PDF] Assessment Report

CO Onyango, Y Suwa, Y Pinto

directory ….. 18 – Table 5: List of ASTI publications in Phase II 3 ….. 20 Table 6: Summary of

ex-post impact assessments by CGIAR Centres, CRPs and SPIA ….. 29

[PDF] Hereditary Immunity against Infectious Diseases

IA Shabarov, ZI Urmancheeva, SN Rumyantsev…

Page 1. 1 Innovative Immunology | Copyright

© Rumyantsev SN.This book chapter is open access distributed under the Creative

Commons Attribu- tion 4.0 International License, which

Encyclopedia of Exploration Geophysics

M this Chapter

Page 1. U1-1 Abstract To produce a reliable image of the subsur- face, we must use

a depth-migration scheme that requires a detailed model of the parameter fields for

use by migration. Obtaining reliable values of all parameters


[PDF] Does “Multiple Labeling” Benefit or Harm in Fibromyalgia Patients

E Trallero, C Alegre – Fibrom open, 2015

A systematic review showed that there is no evidence an accurate diagnosis of fibromyalgia 

per se could worsen prognosis in patients with this condition [1]. Indeed, it could be useful to 

reduce healthcare utilization by patients. Nevertheless, social and individual long-term

[PDF] Comparison between Depression Levels of Women with Knee Osteoarthritis, Rheumatoid Arthritis, and Fibromyalgia Syndrome: A Controlled Study

D Karşılaştırılması, BK Çalışma – 2015

DOI: 10.5152/tftrd.2015.87894 Turk J Phys Med Rehab 2015;61:197-202 Türk Fiz Tıp Rehab 

Derg 2015;61:197-202 Comparison between Depression Levels of Women with Diz 

Osteoartrit, Romatoid Artrit ve Fibromiyalji Sendromlu Kadınlarda Depresyon


CH Lee, K Lee – US Patent 20,150,291,509, 2015

group consisting of dermatitis, allergy, atopy, conjunctivitis, periodontitis, rhinitis, tympanitis,

pharyngolaryngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn’s disease, colitis, irritable

colitis, hemorrhoids, gout, ankylosing spondylitis, lupus, fibromyalgia, psoriasis, arthritis

[PDF] Recent advances in massage therapy–a review

SL LIU, W Qi, H Li, YF WANG, XF YANG, ZM LI, Q Lu… – Eur Rev Med Pharmacol Sci, 2015

in animal models. In a randomized trial conducted by Ekici et al13, application of

MLD to women with fibromyalgia resulted in improvements regarding pain, health

status, and health-related quality of life. Lancaster and Crow14

Immediate Effect of Basic Body Awareness Therapy on Heart Rate Variability

AM Mantovani, CEPT Fregonesi, RMR Lorençoni… – … Therapies in Clinical …, 2015

To determine the immediate effect of a Basic Body Awareness Therapy (BAT) session on

measures of heart rate variability (HRV) in healthy young people.13 healthy.

[PDF] Radial shock wave therapy in the treatment of lateral epicondylitis

JD Rompe, J Decking, C Schoellner, C Theis…

P009-e Gait analysis: An objective measurement for subgrouping fibromyalgia patients B. Auvinet

a,*, D. Chaleil b, J. Cabane c, A. Dumolard d, P. Hatron e, R. Juvin d, M. Lanteri-minet f, Y. Mainguy

g, L. Negre-pages h, F. Pillard i, D. Riviere i, Y. Maugars j a Clinique, 8, rue des


D Brunner, J Malberg, BG Shankar, S Kolczewski… – US Patent 20,150,284,386, 2015

Fibromyalgia, which is a syndrome characterized by chronic generalized pain associated with

different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems,

hypersensitivity to physical and psychological environmental stimuli, depression and


JE Campbell, P Jones – US Patent 20,150,291,626, 2015

affective disorder, seasonal affective disorder, obsessive-compulsive disorder, attention deficit

disorder, attention deficit hyperactivity disorder, vertigo, pain, neuropathic pain, sensitization

accompanying neuropathic pain, inflammatory pain, fibromyalgia, migraine, cognitive

[PDF] How is Qigong Conducive to Women’s Health

FK Cheng – Int J Complement Alt Med, 2015

Likewise, Tai Chi is beneficial for treating fibromyalgia, achieving better symptomatology,

aerobic capacity, dynamic balance, body strength, and walking distance [112]. Psychological

health: Studies inform the effects of Baduanjin on mental well-being.

[HTML] Recommendations to the primary care practitioners and the patients for managing pelvic pain, especially in painful bladder syndrome for early and better prognosis

KJ Chung, ANY Han, KH Kim – Journal of Exercise Rehabilitation, 2015

Scholar]. Nickel JC., Tripp DA., Pontari M., Moldwin R., Mayer R., Carr LK., Doggweiler R., Yang

CC., Mishra N., Nordling J. Interstitial cystitis/painful bladder syndrome and associated medical

conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic


New research reveals that greater frequency and duration of daytime napping are associated with more severe symptomatology in patients with fibromyalgia.

New research reveals that greater frequency and duration of daytime napping are associated with more severe symptomatology in patients with fibromyalgia.

New research reveals that greater frequency and duration of daytime napping are associated with more severe symptomatology in patients with fibromyalgia.


According to the study results, published in BMC Musculoskeletal Disorders (2015 Feb 7;16:13. doi: 10.1186/ s12891-015-0464-y), the majority of participants reported using daytime napping as a strategy for coping with poor sleep and fibromyalgia symptoms. “Participants who regularly took a daytime nap were found to have a higher number of comorbidities, increased levels of pain, fatigue, sleep problems, memory difficulties and mood disturbance in comparison to participants with fibromyalgia who napped less regularly or not at all,” reported Alice Theadom, PhD, senior research fellow at the National Institute for Stroke and Applied Neurosciences, in Auckland, New Zealand.

Whereas previous research has shown sleep to be problematic for people with fibromyalgia, uncertainty remains over whether daytime napping is a beneficial or detrimental coping strategy.

“We found that poor sleep has been linked to poorer outcomes, and we found associations between difficulty falling asleep or waking up during the night with greater levels of pain and fatigue and other symptoms in this condition,” Dr. Theadom stated. “What we were looking at specifically in this study, however, was the impact of how people use daytime naps as a way of managing feelings of fatigue or tiredness during the day.”

An online questionnaire of 1,044 adults who reported napping on a daily basis showed that 18.9% napped in the morning of a typical weekday, 58.8% napped in the afternoon and 25% napped in the evening. It was also revealed that 86.5% of participants found themselves taking a nap without intending to, Dr. Theadom reported.

“Daytime napping was significantly associated with higher levels of pain, feelings of low mood and anxiety, and people feeling more fatigued, as well as memory difficulties and difficulty sleeping at night,” she said. “So daytime napping seemed to be linked to quite a range of symptoms.”

Daytime napping was also associated with a high rate of comorbid conditions, including arthritis (20%), irritable bowel syndrome (15%) and asthma (13%). Of those surveyed, 5.1% reported a psychiatric condition and 11.2% had depression, Dr. Theadom said. Finally, the duration of naps was found to have an influence on the impact of symptoms.
Those who engaged in daytime naps for longer than 30 minutes had greater memory difficulties and levels of depression than those who napped for shorter periods (P<0.010).

The most common reasons for taking a nap included tiredness/exhaustion (94.1%), feeling unwell (67.2%), catching up from the previous night’s poor sleep (59.6%), headache (42.6%) and pain (26.2%).

Although studies of people unaffected by a medical condition have shown a direct correlation between duration of napping and performance outcomes, Dr. Theadom stressed that the data for those with fibromyalgia remain inconclusive. Further research is needed, she said, to understand whether daytime napping is detrimental to symptom severity or whether it can be recommended as a strategy to manage symptoms.

“It’s really important that we try to unpick this so we can make fruitful recommendations to patients who are experiencing difficulties in fatigue,” Dr. Theadom concluded. “We need to provide guidelines so that patients know whether to use the daytime nap or not, and if so, for how long and when.”

“Fibromyalgia is a disorder not only about pain,” said Stuart Silverman, MD, FACP, FACR, former medical director and founder of the multidisciplinary outpatient Fibromyalgia and Chronic Pain Program at Cedars-Sinai in Los Angeles, “but about fatigue, sleep, cognitive dysfunction and also irritable bowel and irritable bladder. People who have more severe fibromyalgia, in terms of decreased functioning, also have more pain, more fatigue, more cognitive problems and more sleep disorders. This study is reinforcing our concept of fibromyalgia as a multisymptom illness. It is more than pain.”
—Chase Doyle

Ketamine May Reduce Chronic Pain in Adolescents

Ketamine May Reduce Chronic Pain in Adolescents

Ketamine May Reduce Chronic Pain in Adolescents


Subanesthetic ketamine infusions are a safe and effective way to relieve chronic pain in adolescents, a new study suggests.

Ketamine, a Schedule III drug, has been used successfully to treat various chronic pain syndromes in adults, according to researchers from Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, in Washington, D.C., who conducted a longitudinal case series to determine the feasibility of ketamine injections in an outpatient setting.

“Our purpose was to look at the clinical outcomes related to our adolescents who were receiving what we considered subanesthetic dosing of ketamine,” said study author Kathy Ann Sheehy, CNS, a nurse specialist at the hospital.

The study included 63 adolescents with chronic pain conditions such as complex regional pain syndrome (CRPS), fibromyalgia and headache, and were treated in the hospital’s tertiary outpatient interdisciplinary Pain Medicine Care Complex from January 2013 to April 2014. The patients received 111 treatments (277 ketamine infusions; maximum dose of 1 mg/kg per hour) during the study period. They were divided into two groups: CRPS (n=23) and all other chronic pain syndromes (n=40). Main outcome measures were self-reported pain scores using a numeric rating scale and morphine-equivalent intake.

The researchers found that ketamine significantly decreased pain scores in 37% of the injections administered. A reduction of 20% or greater was considered significant. Patients with CRPS experienced the greatest reduction compared with the other chronic pain syndromes (P=0.029). The researchers noted that the ketamine infusions did not change the overall morphine-equivalent intake (P=0.3).

“When we looked at the difference between the types of pain syndromes, CRPS was the one that was the most statistically significant as a pain syndrome for reduction in pain scores and reduction in opioid use,” Ms. Sheehy said. “[With] the other pain scores, although overall there was a reduction, we didn’t see a reduction in headaches or other types of complex pain syndromes.”

An analysis of comorbidities showed that:

  • 23% of the patients had psychiatric/psychological disorders (e.g., anxiety, depression, bipolar disorder);
  • 10% had a history of trauma;
  • 10% had postural orthostatic tachycardia syndrome (POTS);
  • 7% had diabetes mellitus;
  • 7% had a malignancy; and
  • 5% had sickle cell disease.

The researchers found that the patients with POTS and trauma experienced the greatest pain reduction and chronic headache patients had the smallest decrease. “Our assumption for that is that both of those are autonomic sympathetic conditions, and most of our CRPS kids actually had trauma,” Ms. Sheehy said.

No adverse events were reported and the ketamine injections were well tolerated, according to the study authors. They said more research on complex pain syndromes, especially CRPS in adolescents, is needed.

Signal Activity Data May Unlock Some Answers Behind Causes of Neuropathic Pain

Signal Activity Data May Unlock Some Answers Behind Causes of Neuropathic Pain

Clinicians seeking greater understanding of the neural activity behind pain can turn to the results of a University of Western Ontario study, which identified variations in neural activity associated with pain processing between control and neuropathic pain groups. These differences in signal activity—particularly in regions critical to endogenous analgesia—may represent a key step in elucidating the pathophysiology that underlies chronic neuropathic pain syndromes.Screen Shot 2015-10-19 at 3.46.52 PM

“Neuropathic pain affects approximately 5% of North Americans, and is considered to be caused by a lesion to the peripheral or central nervous system, trauma or disease,” said Jordan Leitch, MD, a resident at the London, Ontario, institution. “It’s characterized by either spontaneous episodic pain or pathological amplification of pain following a stimulus. In general, neuropathic pain is considered to be an expression of a maladaptive plasticity in the pain system that results in this constant state.”

During testing, functional MRI data were acquired while noxious stimuli were applied at the various pressures the patients had indicated the previous day. The researchers chose standardized pain ratings in lieu of standardized mechanical stimuli because pain response is subjective and varies widely between individuals.

As Dr. Leitch reported at the 2015 annual meeting of the Canadian Anesthesiologists’ Society (abstract 86017), both the volunteers and pain patients exhibited overall positive signal change at a pain rating of 2 and negative signal change at a pain rating of 6 in the midbrain and rostral medulla of the brainstem. However, consistent differences were observed between groups in the ipsilateral dorsal horn of the spinal cord, rostral ventromedial medulla and periaqueductal gray matter—three regions known to play an important role in nociceptive pain processing as well as the endogenous descending modulation of pain.

“In those regions, which we know are associated with ascending nociceptic transmission and the endogenous descending modulation of pain, we’re seeing positive signal change in the control group, but not much of anything in the carpal tunnel group,” she said.

“Another area we found interesting was around the dorsal horn of the cervical spinal cord, which is where the median nerve originates,” Dr. Leitch said. “And in the control group , we saw some variability from baseline, but not much deviation. But when we looked at the carpal tunnel patients, the times that correspond to pain levels 2, 4 and 6 show persistent positive signal changes that don’t follow what we would expect from controls.”

This study, the investigators concluded, is one of the first to identify variations in neural activity associated with pain processing. “I think seeing is believing in terms of pain,” she added. “This could be an important first step in the quantitative assessment of pain, in terms of both the diagnosis and treatment effect. In general, it’s a step towards a method to objectively visualize a sensation that has traditionally been completely limited to our patients’ subjective description.

“Obviously these signal changes are open to interpretation, but they could be the manifestation of the maladaptive plasticity that is postulated to be one of the causes of neuropathic pain,” Dr. Leitch explained. This research may contribute to future studies investigating endogenous analgesia and pain processing in patient groups, which may facilitate the optimization of pain management and improve quality of life for patients suffering from chronic neuropathic pain, he said.

Dr. Leitch was awarded second place at the meeting’s Residents’ Research Competition.

—Michael Vlessides