Pain | Headache NewsBlog

Effects of observational learning on placebo responses, or why sham remedies seem to work so well

By: Dr. Mauskop

19-06-2023

Alternative Therapies, Brain disorders, Chronic migraine, Pain, Pain Research, Psychology of headaches

Many companies selling ineffective treatments for painful conditions manage to attract a large customer base by showcasing testimonials from satisfied customers. Recent research suggests that these individuals might genuinely benefit from hearing others express positive experiences.

A study published in the journal Pain, titled “Learning pain from others: a systematic review and meta-analysis of studies on placebo hypoalgesia and nocebo hyperalgesia induced by observational learning” explores the impact of observational learning on placebo and nocebo responses.

Placebo hypoalgesia refers to when a fake treatment (placebo) reduces pain, while nocebo hyperalgesia is when the placebo actually increases pain. Learning processes, such as classical conditioning and operant conditioning, have been shown to play a role in these effects. Verbal suggestions and observational learning from others also influence placebo and nocebo responses. However, the magnitude of these effects can vary depending on the specific learning process used.

This meta-analysis of 17 studies showed that observational learning can effectively modulate pain and pain expectancies. However, the magnitude of these effects varies across studies. Observing a model in person resulted in larger effects compared to observing a videotaped model. The analysis also suggested that placebo effects can be induced through observational learning, but nocebo effects were not consistently observed. Empathy, specifically the empathic concern component, was found to be associated with the magnitude of observational learning effects.

The article concludes that observational learning can indeed influence pain experience and pain expectancies. Further studies possibly could lead to methods to enhance the treatment effects of proven therapies.

Structural brain connectivity predicts pain

By: Dr. Mauskop

29-05-2023

Head trauma, Headaches, Migraine, Pain, Pain Research, post-traumatic headache

In a recent post, I mentioned a study in which researchers using functional MRI (fMRI) were able to link functional connectivity within the default mode network (DMN) and between DMN and executive control network (ECN) with the degree of disability in migraine patients.

In a new study published in the journal Pain, researchers examined the brains of patients with mild traumatic brain injury (mTBI) using fMRI imaging to understand the brain networks associated with early acute pain following a motor vehicle collision. Here are some key findings:

The properties of the brain’s white matter explained a significant portion of the variation in pain experienced after mTBI. This suggests that certain brain features make patients more likely to report higher levels of pain after the injury.
These white matter connections are associated with physiological and psychological characteristics related to pain sensitivity. The interactions between these connections and parameters of sensory testing and pain sensitivity can explain about one-third of the variability in pain.
The connectivity patterns in the brain’s white matter do not change over time, as observed up to a year after the injury. The same connectivity measures collected shortly after the injury and at six months post-injury can predict the level of pain reported by patients at the six-month mark.
The study further indicates that the strength of white matter connections in the sensorimotor, thalamic-cortical, and default-mode networks is associated with pain severity. These findings highlight the involvement of these brain networks in pain perception and suggest that connections within these networks can influence the experience of pain.

Over the past decade, scientists have been increasingly interested in functional connectivity, which is a way of finding networks in the brain that are related to particular activities, including resting. One of the most prominent networks is the default mode network.

The DMN is most active when the brain is at rest. When the brain is directed towards a task or goal, the default network deactivates. The DMN involves low-frequency oscillations of about one fluctuation per second.

The DMN is thought to be involved in a variety of cognitive functions, including self-awareness, social cognition, memory, thinking about the future, and daydreaming. The DMN is also thought to be involved in some psychiatric disorders, such as depression, post-traumatic stress disorder, obsessive-compulsive disorder, schizophrenia, and others.

The findings of this study suggest that the brain’s white matter networks plays an important role in pain perception, and that understanding these brain-pain relationships may lead to new treatments for pain in individuals with mTBI.

These brain networks are not fixed and we already have tools to improve their function. Meditation is one of the most effective and accessible such tools. Meditation has been shown to increase connectivity between different brain regions, including those involved in pain perception. It has also been shown to reduce the activity of pain-related brain regions. In addition to meditation, other things that people can do to improve the function of their brain networks and reduce pain include exercise and sleep.

Antidepressant use during pregnancy

By: Dr. Mauskop

30-04-2023

Brain disorders, Chronic migraine, Headache medications, Headaches, Headaches in children, Migraine, Pain, Psychology of headaches

Antidepressants are commonly prescribed to treat migraines, tension-type headaches, and various types of chronic pain. Migraines primarily affect women of reproductive age, and those who suffer from migraines are more likely to develop anxiety and depression compared to those without migraines. This may be another reason why someone with migraines might be prescribed an antidepressant. Women who are pregnant or planning to become pregnant are understandably cautious about taking any medication.

Antidepressant use during pregnancy does not increase the risk of neurodevelopmental disorders in children, according to a new study published in JAMA Internal Medicine.

Antidepressant use during pregnancy has been associated with neurodevelopmental disorders in children in some studies. However, other factors such as the parent’s mental health status, genetics, and environmental factors may have influenced these results. The objective of this study was to evaluate the association between antidepressant use in pregnancy and neurodevelopmental outcomes in children.

The study looked at data from over 3 million pregnancies, tracking children from birth until outcome diagnosis, disenrollment, death, or the end of the study (maximum 14 years). There were 145,702 antidepressant-exposed pregnancies.

The study found no evidence to suggest that antidepressant use in pregnancy itself increases the risk of neurodevelopmental disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder, specific learning disorders, developmental speech/language disorders, developmental coordination disorders, intellectual disabilities, or behavioral disorders.

However, given the strong crude associations found in previous studies, antidepressant exposure during pregnancy may be an important marker for the need for early screening and intervention to modify factors that do increase such risk.

How to reduce pain recollection

By: Dr. Mauskop

24-04-2023

Brain disorders, Headaches, Migraine, Pain, Pain Research, Psychology of headaches

A recent study published in the journal Pain showed that adding a non-painful stimulus at the end of a Pap smear can reduce pain recollection. The study, titled “Adding a Nonpainful End to Reduce Pain Recollection of Pap Smear Screening: A Randomized Controlled Trial,” was conducted by Taiwanese researchers and involved 266 women.

The study involved an intervention group that received a modified Pap test, where the operator kept the speculum still in the vagina for an additional 15 seconds after rotating it back, instead of immediately removing it. Participants in the modified Pap test group were unaware of this additional step, as they were behind a privacy curtain.

The outcomes of the study included recalled pain after Pap smear screening, real-time pain, and 1-year willingness to receive further Pap tests. Among 266 subjects, the modified Pap group experienced lower 5-minute recalled pain than the traditional Pap group on a 1 to 5 numeric scale and on a 0 to 10 visual analog scale. Subgroup analyses showed that these results were not affected by predicted pain, demographic, or socioeconomic characteristics, but it was more apparent in postmenopausal women. Additionally, the modified Pap test attenuated 1-year recalled pain on both pain scales and increased the 1-year willingness grade to receive further Pap tests.

This technique could potentially be applied to many other painful procedures, including Botox injections, blood draws, vaccine injections, dental procedures, and more.

Using AI to predict who will respond to placebo

By: Dr. Mauskop

16-04-2023

Headache medications, Headaches, Pain, Pain Research, Psychology of headaches

Placebo response is a bane of clinical trials but it can be very helpful in practice. A team of American and Canadian researchers used AI to help identify predictors of the placebo response. The results were recently published in Pain, under the title, Predicting placebo analgesia in patients with chronic pain using natural language processing: a preliminary validation study.

Since they used AI for their study, I thought it would be fitting to use ChatGPT to edit their abstract for the lay public.

Patients with chronic pain often experience significant pain relief from placebos (inert pills), and this effect can last for days or even weeks. However, it’s still unclear whether we can reliably predict who will respond to placebo and how to do so. Previous research has shown that people who respond well to placebos tend to talk about their pain and their life in a certain way. In this study, the researchers looked at whether these language patterns can predict who will respond to a placebo before they even receive the treatment, and whether we can distinguish between people who will respond to a placebo versus a real drug.

To do this, they analyzed language patterns from patients with chronic back pain who received a placebo in one study and used this information to build a language model that could predict who would respond to a placebo in a separate study. They found that this language model was able to predict, before treatment, which patients would respond well to a placebo in the second study. These patients reported an average of 30% pain relief from the placebo, while those predicted to be non-responders only experienced a 3% reduction in pain. However, the model was not able to predict who would respond to a real pain medication or who would recover without treatment, suggesting that it specifically predicts response to placebos.

Overall, this study suggests that we may be able to use language patterns to predict who will respond to placebos, which could help researchers design better clinical trials and improve patient care.

GABA supplement for anxiety and insomnia

By: Dr. Mauskop

05-02-2023

Alternative Therapies, Headache medications, Pain, Science of Migraine

GABA, or gamma-aminobutyric acid, is a popular supplement for the relief of anxiety and insomnia. Until recently, I was not recommending it to my patients. There are no scientific studies showing that it works. So why did I start recommending it? A report by a single patient, or as we say in scientific literature, an N of 1.

This 65-year-old woman had been suffering from anxiety from a young age. When her summer camp friends would write down everyone’s most common sayings, hers was, “I am so nervous”. This sense of anxiety persisted throughout her life. She is a successful career woman with a loving family. After a death in her family, she started seeing a psychologist who suggested taking GABA for insomnia. Within days, she was overcome by a sense of calmness she never experienced in her life. It’s been several months now and she remains calmer than ever before.

Certainly, this could be a placebo effect. In addition to the lack of controlled clinical trials, it is not even clear if GABA gets into the brain by crossing the so-called blood-brain barrier (BBB). It is possible, however, that it does not have to cross BBB. There is evidence that GABA may work through the enteric nervous system (ENS) – nerve endings lining the intestines. Both GABA and its receptors are widely distributed in the gut. Certain probiotics such as Lactobacillus and Bifidobacterium were found to increase GABA concentrations in the ENS. Probiotics have been shown to improve mood. This effect may be occurring through the vagus nerve. Vagus nerve is a large nerve that connects the intestines and all internal organs with the brain. It was somewhat of a surprise that vagus nerve stimulation at the neck level was proven (and FDA-approved) to relieve refractory depression and epilepsy.

GABA has been a popular supplement for many years. This obviously does not prove that it really works. However, it is very safe and relatively inexpensive. I would consider trying it before taking a prescription drug for anxiety or insomnia. Those can have significant side effects and in a 65-year-old may increase the risk of Alzheimer’s disease. And I always recommend regular exercise and meditation before any supplements.

Botox for trigeminal neuralgia due to multiple sclerosis

By: Dr. Mauskop

07-01-2023

Botox, Brain disorders, Pain, Trigeminal and other neuralgias

Botox has been shown to relieve the pain of trigeminal neuralgia (TN). TN is an excruciatingly painful and debilitating condition. The most common cause of TN is compression of the trigeminal nerve by a blood vessel. This tends to occur in older people in whom blood vessels may harden with age. The definitive treatment of TN is surgical decompression of the trigeminal nerve. This is done by opening the skull and placing a Teflon patch between the nerve and the blood vessel. Several medications and invasive procedures directed at the peripheral nerve have been also proven effective. They are usually tried before surgery because of the risk of complications from surgery.

Besides the elderly, younger people with multiple sclerosis (MS) are also predisposed to developing TN. The mechanism is somewhat different. There is less or no compression of the nerve but rather there is damage to myelin, a sheath that covers the nerve inside the brainstem. Myelin prevents cross-talk between nerve fibers, which is the cause of the pain.

According to a report by Turkish neurologists that was recently published in Headache, Botox can relieve the pain of TN in MS patients as well. They compared the response to Botox in 22 patients with primary TN and 31 with MS-related TN. Ten patients of 22 in the first group and 16 out of 31 in the second group improved with Botox. Patients who had interventional treatments in the past did not respond as well. Those who had mild continuous pain between bouts of severe pain were more likely to respond to Botox.

Botox is not the first-line treatment for TN. Medications such as carbamazepine and oxcarbazepine are. However, Botox is a very safe treatment and should be tried before considering surgery and other invasive procedures.

Microdosing for chronic pain

By: Dr. Mauskop

14-11-2022

Alternative Therapies, Chronic migraine, Headache medications, Headaches, Migraine, Pain, Pain Research

Psychedelics are being actively studied for depression and post-traumatic stress disorder (PTSD). These trials usually involve hallucinogenic doses. Microdosing psychedelic substances such as psilocybin, lysergic acid diethylamide (LSD), and methylenedioxymethamphetamine (MDMA) has become a popular treatment for depression. Microdosing means that the amount of a psychedelic is too low to cause hallucinations or other overt sensory experiences.

There is an accumulation of evidence that psychedelics can provide pain relief. A case series just published in the journal Pain describes three patients with chronic pain who obtained significant relief from microdosing psilocybin-containing mushrooms.

The first patient was a 37-year-old man with severe pain due to traumatic quadriplegia. He had almost complete relief of pain and was able to stop taking tramadol, an opioid analgesic, diazepam (Valium), and marijuana. The relief was ongoing for six months when he was last seen by the doctors.

The second patient was a 69-year-old woman with complex regional pain syndrome (also known as reflex sympathetic dystrophy) secondary to left leg trauma. She had tried nerve blocks, other invasive procedures, stem cell injections, acupuncture, opioid analgesics, and many other medications, all with no relief. At the time of the published report, microdosing was providing continued significant relief for over a year.

The third patient was a 40-year-old woman with pain in her leg due to degenerative disk disease in her spine. Her pain did not improve with epidural injections, back surgery, muscle relaxants, opioid drugs, and physical therapy. Psychedelic mushrooms had a profound effect on her pain.

Psychedelic mushrooms have been reported by many patients to be effective in the treatment of cluster headaches (see ClusterBusters.org). A small double-blind study by Yale researchers showed a beneficial effect of synthetic psilocybin in treating migraine headaches.

It remains to be proven that sub-hallucinogenic doses of psychedelic drugs provide relief of painful conditions. If proven effective, however, such drugs will offer a much safer option than any opioid and NSAID analgesics, epilepsy drugs, antidepressants, or any other prescription drug. They are very safe even at hallucinogenic doses.

I am often asked about the practical side of using psychedelic mushrooms – where to buy them, how much to take, and for how long. Since the state of NY, unlike some other states, has not legalized or decriminalized the use of psychedelic mushrooms, I cannot answer these questions. Even if it was legal for me to do, I would not have reliable answers until clinical trials give us good data.

Daxxify, a new Botox competitor

By: Dr. Mauskop

08-09-2022

Alternative Therapies, Botox, Chronic migraine, Headache medications, Headaches, Migraine, New treatments, Pain

No, Daxxify is not really a competitor in the treatment of chronic migraines or any other medical condition. Daxxify, a new botulinum toxin, was just approved by the FDA only for cosmetic use. Daxxify does stand out from five other botulinum toxin brands in that its effect lasts longer. The other toxins are Xeomin, Dysport, Jeuveau, and Myobloc. Myobloc is approved only for medical conditions, Jeuveau only for cosmetics, and Xeomin and Dysport are approved for both cosmetics and a few medical conditions.

Initially, Botox was approved by the FDA in 1989 to treat eye problems. Since then, it has been approved for many medical and cosmetic indications, including chronic migraine. None of the other toxins are approved for such a wide range of indications. It remains by far the most widely used type of botulinum toxin with tens of millions of people treated for medical and cosmetic reasons.

Yes, having a longer-acting botulinum toxin is an advantage. You will need to have less frequent treatments. However, if you have any side effects, they will also take longer to go away. We are talking mostly about cosmetic side effects, such as droopy eyelids. When treating headaches, with proper technique, side effects are uncommon. These may include weakness of the neck muscles or, if treating TMJ syndrome, difficulty chewing.

Since Botox is approved by the FDA for chronic migraines, Botox is the drug insurance companies cover. Allergan (a division of Abbvie), the manufacturer of Botox, has many more years left on their patent to treat chronic migraines. Botulinum toxin is a biological product (made by bacteria rather than synthesized from chemicals) and every version of it is slightly different. This is why when Allergan’s patent to treat migraines expires, the competitors will have to conduct large trials to prove that their product is also effective for migraines.

Rimegepant for trigeminal neuralgia: a case report

By: Dr. Mauskop

18-07-2022

Brain disorders, New treatments, Pain, Trigeminal and other neuralgias

A case report presented at the annual meeting of the American Headache Society described a patient with trigeminal neuralgia (TN) whose pain responded well to rimegepant (Nurtec). Rimegepant is a drug approved for the acute and preventive treatment of migraines. This patient did not obtain relief from surgery and several medications. He was taking 300 mg of oxcarbazepine, buprenorphine (narcotic) patch, and up to 120 mg of oxycodone with partial relief. Within 12 hours of starting rimegepant he was pain-free. In the six months of taking rimegepant he experienced very infrequent and mild pain.

There have been several reports indicating that injections of CGRP monoclonal antibodies such as erenumab can relieve the pain of TN. So it is not surprising that an oral CGRP drug helped this patient.

I’ve treated several TN patients with CGRP antibodies. One such patient has been receiving injections of galacanezumab for over 3 years. He requires injections of 240 mg every 3 weeks and also has to take daily medications. This combination has allowed him to be fully functional and to keep his job. I may now try him on an oral CGRP drug.

In addition to rimegepant, there are two other oral CGRP drugs – ubrogepant (Ubrelvy) and atogepant (Qulipta). They are very similar but many patients have a clear preference for one over the others. It may be worth trying them all if the first drug is not fully effective. A major obstacle to using these medications “off label” for TN is their high cost.

Internet-delivered cognitive and behavioral interventions help chronic pain

By: Dr. Mauskop

05-02-2022

Alternative Therapies, Pain, Pain Research, Psychology of headaches

My previous post described a study that found no difference in efficacy among different types of psychosocial interventions for the treatment of chronic back pain. A recent 2020 Cochrane review concluded that there is strong evidence that face-to-face treatments based on cognitive behavioral therapy (CBT) have a small beneficial effect on reducing pain, disability, and distress in people with chronic pain.

A meta-analysis just published in the journal Pain examined the efficacy of CBT delivered via the internet. Australian researchers examined 36 studies with 5778 participants. Most participants were female, and most studies recruited participants from community settings through online advertisements in Western countries.

They concluded that “internet-delivered cognitive and behavioural interventions can result in small significant improvements in interference/disability, depression, anxiety, pain intensity, self-efficacy and pain catastrophizing. Guided interventions may result in greater treatment effects for key outcomes in pain management, including interference/disability, anxiety and pain intensity.”

The meta-analysis showed that guidance by a clinician improves the results. However, this guidance varied across the studies in terms of
how it was provided (e.g., via secure email, SMS messages, telephone calls), the timing and frequency with which it is provided (e.g., weekly, on demand, or at set time points), the amount provided (e.g., brief versus extended), and the professional qualifications and experience of those providing it (e.g., students-in-training, registered psychologists, non-health professionals). There was no difference between the traditional CBT and ACT (acceptance-commitment therapy), confirming the results described in my previous post.

There are several sites that offer CBT courses over the internet. ThisWayUp.org.au and moodGYM.anu.edu.au, online-therapy.com, and others. During the pandemic almost all social workers and psychologists switched to virtual appointments. Lower cost is the advantage of self-directed online CBT courses.

Marijuana increases the risk of car accidents

By: Dr. Mauskop

13-01-2022

Alternative Therapies, Brain disorders, Migraine, New treatments, Pain

I’ve been prescribing medical marijuana (MM) since 2016 when it became legal in New York. We still lack controlled clinical trials of MM for the treatment of migraines. Most of my patients who find MM useful report that it relieves nausea or anxiety, helps them go to sleep and sometimes relieves pain. Others find that taking it daily prevents migraines. CBD alone can be also helpful, but most patients need a combination of CBD and THC as well in order to obtain a therapeutic effect.

Like any other drug, MM can have side effects. One of them is cognitive impairment. A study just published in the New England Journal of Medicine describes the effect of recreational marijuana legalization in Canada on injuries to car drivers. The researchers studied drivers treated after a motor vehicle collision in four British Columbia trauma centers from 2013 through 2022. They discovered that after legalization, the number of moderately injured drivers with a THC level above the legal limit doubled. The largest increase was seen in older and male drivers.

This is relevant to the users of MM as well. From now on, I will caution my patients not to drive after taking any THC-containing products. Just like with alcohol, you don’t need to have a blood level above the legal limit to slow your reflexes.