There are many kinds of pain—Piercing, burning, aching, shocking—but the type I want to focus on today is throbbing. Throbbing pain is often associated with toothaches, headaches, migraines, and pain in the extremities but can occur nearly anywhere in the body. Its pulsing nature can be incredibly annoying to those affected, but it also raises an interesting question: when pain throbs, what rhythm is it following?
Contrary to what you might think, throbbing pain is not beating to your heartbeat or pulse. A 2012 study looked at the throbbing rate of 29 dental patients’ pain, as recorded by patients pushing a button every time they felt a painful throb, compared to their arterial pulse measured in their earlobes. The mean arterial pulse rate was 73 beats per minute (bpm), compared to a throbbing pain rate of just 44 bpm. Researchers further analyzed the simultaneous recordings and found that the two rhythms weren’t synchronous in any way.
If throbbing pain isn’t paced against our heartbeat or pulse, then what determines its rhythm? Simply put, we don’t know! The study’s authors theorize that the pacemaker of throbbing pain is contained somewhere within the central nervous system, but we currently do not have any more specific theories. For now, we just have to accept that throbbing pain marches to the beat of its own drum.
Shots, jabs, pricks—whatever you call it, having a needle inserted into your body is not most people’s idea of a fun afternoon activity. Even if you don’t have a specific needle phobia, injection reactions typically range from neutral at best to quite negative at worst. But what if needles didn’t have to hurt? Or, at least, what if they hurt less? It seems intuitively true that decreasing the size of a needle would make it hurt less, but is it really that simple?
The diameter of a needle (how big it is across) is measured in a unit called a gauge. Because the concept of a gauge pre-dates the 18th century and has been defined in many different, inconsistent ways, it’s worth specifying that needle width is measured in the Birmingham gauge. The bigger the gauge, the smaller the needle. For example, the width of a 7-gauge needle is roughly 4.6 mm (0.18 inch), while the width of a 30-gauge needle is about 0.31 mm (0.012 inch). To give you some context, a typical spaghetti noodle is roughly 14-gauge, and a regular stud earring is about 19-gauge.
There are a few factors that determine what size of needle a practitioner needs to use, including the body size of the patient and the body part being pricked, but a critical factor is the amount of fluid being injected or drawn out of the patient. If you try to inject a large amount of fluid through a very thin needle, it will both take longer and hurt more due to the high pressure.
For blood collection, which is typically a few millilitres of blood, clinicians use needles of 21-22 gauge. Vaccines are often <1 mL and accordingly use needles that are slightly smaller, around 22-25 gauge. Delivering insulin to diabetic patients requires even less fluid and can use needles as small as 29-31 gauge.
Even with the limitations imposed by volume, there is some wiggle room in the gauge of needle used for a certain procedure. Medical practitioners can often use their own judgment, experience, and clinical guidelines to change the size of needle they use. Much like how artists may favour a certain size brush, some clinicians have personal preferences in the tools of their trade.
Luckily, it is actually relatively simple to study whether decreasing needle diameter decreases pain. Just find some volunteers who are willing to be stabbed for science (or who are already being treated with a needle-involved method), stick them with at least 2 needles of different gauges without telling them which is which, and ask them how much it hurt on a numeric scale. There are dozens of studies that take this form.
Regarding simple injections in the body, this study compared a 30-gauge needle with a 26-gauge one and found no significant difference in the reported pain. As did this study, which compared 27-gauge vs 23-gauge vs 21-gauge. For injecting Botox around patients’ eyes, this study found no difference in pain scores between a 32-gauge and a 30-gauge needle. These are by no means all of the studies on needle size and pain, but they are representative of the scientific literature on this topic. Again and again, trial participants seem to find no significant difference in their pain when comparing needle gauges.
For many people, the anesthetic injection is the worst part of any dentist visit. While it would be lovely to tell you that a quick swap to a thinner needle is all you need to decrease the pain of dental injections, there is a wealth of evidence to the contrary. For anesthetic injections in the mouth, smaller-width needles were not only ineffective at reducing pain; in one study, they actually increased it!
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NEM, or Natural Eggshell Membrane has popped up as a popular supplement for osteoarthritis sufferers. The companies selling it boast claims about relieving joint pain and improving the user’s range of motion in just a week! The pills aren’t especially expensive, costing only about $0.50 – 1.00 a day, but the question is whether or not they work.
NEM is said to act as a source of collagen, glucosamine, chondroitin, hyaluronic acid, and calcium, all of which have been investigated extensively for osteoarthritis treatment.
Collagen is the much-hyped novel treatment for everything from arthritis to wrinkles, but there is not much evidence to support these claims. While it plays a very important role as a component of joints, cartilage and ligaments, oral collagen supplements are not likely to mitigate joint pain. There have been several studies done on arthritic mice that show positive results, as well as some on arthriticdogs, but there is a lack of relevant human studies. Glucosamine and chondroitin have been thoroughly studied and have been found to lack efficacy in the vast majority of osteoarthritis patients. As far as hyaluronic acid goes, taking oral supplements is probably useless.
Calcium supplementation is recommended for patients with osteoporosis (if they aren’t getting enough dietary calcium), but patients with this condition are unlikely to also experience osteoarthritis, rendering calcium supplementation moot.
So, the individual constituents of NEM don’t help much, if at all. But what about a combination of these elements?
We have previously addressed Joint Ease Plus, a supplement marketed for arthritis that contains many of the same constituents as NEM. The studies used to support the claims of this supplement were unpublished and sketchy to say the least.
At least NEM has current, properly conducted studies on its efficacy. So, what do they say?
Testing any supplement for benefits usually begins with looking for effects in rats or mice. Unlike with human subjects, keeping the rats blinded to what substance they’re receiving isn’t relevant, but other tenets of a successful study, like large sample sizes, still apply.
In scientific studies we want to rule out the possibility that results may have occurred due to random chance and we look for “statistical significance” meaning that the results seen were due to whatever intervention was carried out.
Here are some studies that have been carried out in a reasonable fashion.
This study showed a reduction of some inflammatory cytokines when NEM was given in doses of 6.13-52 mg/kg of body weight (equivalent to 59-503 mg per day in a 60 kg person), but their sample size was low, only 3 rats for the lower doses and 8 for the higher. This study found similar results, but only used 7 rats.
This study looked at NEM in conjunction with goat fat as a source of omega-3 fatty acids in a range of doses, and found positive results based on knee diameter (a marker of swelling) and animal behaviour, albeit using sample sizes of 5 per dose.
This study used a sample size of 54, and found similarly positive results in reduction of ankle diameter, lower ankle and knee histopathology scores and lowered the amount of pro-inflammatory cytokines found in the blood.
However, it’s hard to say whether a supplement giving statistically significant results in rats will give statistically significant results in humans (their biology is similar but not the same). Furthermore, it’s even harder to say whether those results in humans will be clinically significant. You could have a reduction in pain that, while statistically significant, is too miniscule to matter to a patient. That’s why testing on humans is the important criterion.
So, onwards to the human studies.
This study involved 37 patients and gave them 500 mg of NEM daily for 8 weeks. Based on questionnaires in which patients rated their pain on a scale of 1-10, statistically significant results ranging from 22.4% to 35.6% improvement were seen. That means that with the best results patients went from rating their pain on average a 3.4 to a 2.2 out of 10. It’s not nothing, but it’s not a miracle cure either.
But (there’s always a but), this study lacked the very important placebo control. Without that it’s impossible to say whether NEM works any better than a sugar pill, and this is especially important since glucosamine just barely works better than a placebo.
This study was placebo controlled, and double blind. It involved 25 patients, 13 of which were treated with 450 mg per day of BiovaFlex® (made from water soluble egg membrane), the other 12 with a placebo. Sadly, the study doesn’t actually tell us what is in BiovaFlex®. Their website mentions collagen, elastin and a few other ingredients, but still doesn’t give amounts. So, even though the study showed pretty good results, like a 45% pain reduction in upper back pain at rest with BiovaFlex® vs. 23% reduction for placebo, we can’t really derive anything from this study except that BiovaFlex® works decently. Of course, the company also sponsored the study, so take these results with a grain of salt.
This study was also placebo controlled, and double blind, with 31 subjects receiving placebo and 29 subjects receiving 500 mg NEM daily. However, there was a roughly 40% dropout rate. That doesn’t discount the trial, but it doesn’t bode well, considering 9 patients receiving NEM dropped out due to a lack of efficacy. Still, with those remaining subjects, the study found statistically significant results for reductions in pain and stiffness at 30 and 60 days post treatment, but insignificant results for an improvement of function or overall joint health.
Another study found that NEM aids in joint recovery when given in 500 mg doses to healthy postmenopausal women who experiences low levels of pain (less than or equal to a 3/10), but that’s hardly the target audience for joint pain reduction.
Perhaps the most interesting of the studies, this one examined the efficacy of NEM in general, as well as the degree to which hydrolysis of eggshell membrane prior to blending into supplement form may affect its effects. It first used 11 patients to test 500 mg of daily NEM and found reductions in overall pain relevant only after 30 days, but an increase in flexion significant after 7. The most striking result was a 75.9% improvement in range-of-motion related pain after 30 days. The researchers then compared a 2.5 x more hydrolyzed version of NEM with the normal version and found (using 14 subjects) that the more hydrolyzed version doubled the percent improvement of patients (18.4% vs 31.3%). These results seem to hugely support NEM as a supplement, specifically a more hydrolyzed version of it (they never discuss what effect the increased hydrolysis has on the supplement, but it likely breaks proteins down further and facilitates their absorption). However, this study wasn’t blinded, wasn’t placebo controlled, and most importantly the patients tested didn’t have arthritis. Those recruited only needed to rate their pain as 2/10 to qualify as subjects.
These results are all pretty lackluster and point to NEM helping only minimally with pain and stiffness, both in those with and without arthritis. Arthritis supplement studies in general show us how statistical significance and clinical significance are not the same thing.
On a positive note however, NEM is safe. No study found adverse effects as exemplified by this study on its safety which found no toxicity at doses up to 2000 mg/kg body weight per day in rats.
Bottom line: The evidence for Natural Eggshell Membrane helping with arthritis is pretty thin.
Cissus quadrangularisis a plant which belongs in the grape family, has red berries, and green or yellow flowers. Cissus quadrangularisis also the name slapped across a lot of supplements that claim to support ‘optimal joint health’, ‘promote healthy bone structure’, and support ‘healthy weight management’. Add in a few anti-ulcer properties, a pain-killing effect and even type II diabetes support, and this all sounds too good to be true. And it is right?
Well, as per usual, there’s some truth to this plant’s claims, and a lot of overblown and overhyped information.
Cissus quadrangularishas been used for centuries in the traditional medical practices of India. It’s used as a pain reliever, and to heal broken bones. Indeed one of its many names is asthisamharaka, which translates to ‘that which prevents the destruction of bones’.
There are a lot of claims about C. quadrangularis(CQ), but we can broadly divide them into a few different groups, its action as an: analgesic (pain relieving), anti-inflammatory, antioxidant, bone growth supplement and weight loss supplement. Let’s unpack these one at a time.
There have been a few studies looking at the potential pain relieving effects of CQ. A 2010 study looked at the ability of CQ supplements to inhibit pain in rats. They compared 50, 100 and 150 mg/kg bwt (body weight) of CQ with 300 mg/kg bwt of aspirin, and found CQ to be more effective than aspirin at 150 mg/kg bwt. A 2008 studylooked at CQs analgesic effects in albino mice, and found that at doses of 250 or 350 mg/kg bwt CQ worked to inhibit both neurogenic pain (pain from damage to nerves) and inflammatory caused nociceptive pain (pain resulting from injury). The extra 100 mg/kg bwt of CQ caused a ~10% increase in pain tolerance, in both types of pain. A 2008 studyechoed the finding that CQ acts as an analgesic, and suggests ‘the analgesic activity may be due to the presence of carotene, phytosterol substances, calcium, sitosterol, amyrin and amyrone’.
Most analgesics also have some anti-inflammatory action, and it seems that CQ is no different. This 2007 study looked at the supplement’s analgesic, anti-inflammatory and venotonic (increasing venous blood flow) effects, specifically in how they may be used to treat hemorrhoids, and rules positively. The same studythat looked at pain in rats also examined CQ’s ability to act as an anti-inflammatory and an antipyretic. As an anti-inflammatory, 150 mg/kg bwt CQ was more effective than 300 mg/kg bwt aspirin for the first 3 hours after administration. After this time, CQ lagged behind aspirin, but only slightly. As an antipyretic, CQ in the doses tested (50, 100, 150 mg/kg bwt) was less effective than aspirin, but still showed ‘marked’ antipyretic effects.
As far as antioxidant action goes, CQ seems to fair quite well. This 2010 studynotes CQ’s efficacy at lowering lipid levels, improving insulin sensitivity and general antioxidant protection. A 2006 study examined CQ’s potential in treating ulcers caused by NSAIDs (like Advil). In doses of 500 mg/kg bwt, CQ was shown to ‘effectively reduce the extant of gastric lesions’ when used before aspirin treatments. The antioxidants in CQ allow it to enhance ‘defence enzymes in gastric mucosal tissues’. It’s theorized that CQ acts by inhibiting the formation of pro-inflammatory cytokines (substances that tell the body to become inflamed), but no studies that I could find seem sure of the mechanism of CQ’s ulcer defence. They do, however, seem fairly sure that it works.
This 2004 study noted that CQ supplementation caused an increase in mucous secretion in the stomach, and an increased concentration of mucin, the major protein constituent, in that mucous. It also noted a decreased number of shed cells, and an increase in the DNA per mg of mucous, both of which signal healthier stomach lining. Another 2006 studymirrored the ulcer-healing properties of CQ, and suggested that the high β-carotene content of the plant is responsible for its antioxidative properties.
Speaking of healing things, why not bones too? This 2003 studyfound that treatment with 750 mg/kg bwt CQ per day for 3 months caused a significant increase in osteoblastic (bone cell formation) and decrease in osteoclastic (bone cell re-absorption) activity. It suggests that an unidentified anabolic phytogenic steroid is responsible for CQ’s osteoporosis fighting capability. This 2009 studymimics the preventative effects of CQ on bone loss, and postulate that its effect is due to the steroids interacting with estrogen receptors. A different 2009 studygave perhaps the most in depth analysis of CQ’s method of action. It found that CQ activated and sped up the process of turning bone marrow stem cells into osteoblasts (bone cells).
Now for the claim that seems to be the odd one out, CQ’s effectiveness as a weight loss drug. This 2006 studyfound that at daily doses of 1028 mg for 8 weeks, CQ combined with green tea, soy, B vitamins, selenium and chromium reduced ‘weight, % body fat, BMI and, especially, waist circumference of obese and overweight patients, regardless of calorie-controlled diet’. A 2008 studyconfirmed these results, and specifically found that a combination of CQ and Irvingia gabonensis (African Mango) positively affected patient’s weights and other parameters of metabolic syndrome.
So how can one plant be having this many effects? Well, that remains to be seen. When researching CQ I found an abundance of studies, without an abundance of answers, and I expect more research to be done in the future. We do knowhowever a lot of the constituents in CQ, such as ‘flavanoids, triterpenoids, Vitamin C, stilbene derivatives, resveratrol, piceatannol, pallidol perthenocissin and phytosterols’. We know that ‘the plant contains ascorbic acid, 479 mg and carotene, 267 mg per 100 g freshly prepared paste, in addition to calcium oxalate’, and that ‘the root powder also contain a rich source of mineral elements (mg/100g dry matter): potassium 67.5, calcium 39.5, zinc 3.0, sodium 22.5, iron 7.5, lead 3.5, cadmium 0.25, copper 0.5 and magnesium 1.15’.
We need to be careful though not to fall into a trap of seeing a long list of chemical names and assuming it’s a new wonder drug. Some of these things are known to be beneficial to humans (like vitamin C), others have more debated effects (like resveratrol), and like every drug, dose matters. It doesn’t matter is CQ has pallidol, if it’s not in relevant amounts. Almost every study that I cited here ends with some variation of ‘further work is necessary to isolate active principles and elucidate the actual mechanism involved in the antioxidant activity of this plant’, meaning that even in the face of these results, these studies know that research is crucial to fully understand this supplements, before we can recommend it for humans. Not to mention that the majority of studies mentioned here were performed on rats or mice, and though they’re good human analogues, they are not perfect replicas.
There is also potentially some behind the scenes meddling at play in these remarkable findings. As this 2010 journal letterpoints out, ’at least 3 recently published studies support the safety and effectiveness of CQ for weight loss but lack financial disclosures or funding sources’. It’s a common practice for studies to mention their funding sources, whether they be McGill University, Government of Canada, or the Liquor Control Board of Ontario. Stating where the money comes from for a study allows readers to know if any involved parties have vested interests, as some CQ study authors seem to. The 3 aforementioned studies have an author in common, who holds the patent for Hydroxycut Advanced, a weight loss supplement using CQ. If that’s not a conflict of interest, then I’m not sure what is.
Looking at the studies of CQ, I’d be hard pressed to deny its potential for use in the treatment of a variety of illnesses, but looking at the state of CQ research right now, I wouldn’t add it to my Amazon cart just yet.
Ada McVean 