Hypodermic needles come in a dizzying array of options in terms of sizes and point styles, but fundamentally not much has changed since they really hit the scene over a century ago. Many of us are lucky enough not to require too many injections in our lifetime, but for some the pain of being stabbed with a needle is a daily misery, making compliance with injected therapies a real challenge. Understanding the mechanics of how needles actually penetrate the skin can help us create less painful needles and, as ever, nature can provide some inspiration. But to really reduce pain, we may need to look beyond the needle…
Sir Christopher Wren: possibly the most highly acclaimed British architect in history, genius behind some of London’s most iconic buildings, and fan of getting his dog drunk in new and interesting ways.
While taking part in medical experiments at Wadham College, Oxford, in 1659, Sir Christopher wanted to know if drugs usually administered orally would have the same effect when administered intravenously. His method: inject wine and ale into a dog’s veins and measure its intoxication, occasionally mixing things up a little and injecting opium1. His injection apparatus of choice consisted of an animal bladder acting as the syringe and a goose quill acting as the needle, and he is now widely accredited with the first successful injection of a substance into the bloodstream.
However, Wren’s was not the first hypodermic needle. In the 11th Century, the Iraqi physician Ammar bin Ali Mawsili described removing soft cataracts using a thin, hollow metal tube. In doing so he invented the process of removing cataracts by suction, a technique still used today.
Sir Christopher Wren: possibly the most highly acclaimed British architect in history, genius behind some of London’s most iconic buildings, and fan of getting his dog drunk in new and interesting ways.
Swiftly following Wren’s experiments, others experimented with injecting substances into humans, but their efforts were usually ineffective or fatal. Injection was not picked up again in earnest until the 19th Century when drugs that were effective in small doses, such as opiates and strychnine, were developed.
In the 1850s, the Scottish Doctor Alexander Wood developed a syringe with a hollow needle fine enough to pierce skin (Charles Gabriel Pravaz is also credited with independently inventing a hypodermic needle at the same time). Wood’s primary interest was the delivery of localised anaesthesia, and as well as developing the syringe as we recognise it today, he and his wife may also have invented injected morphine addiction, the unfortunate Mrs Wood becoming the first ever recorded case of accidental injected opiate overdose.
By the late 1800s hypodermic syringes were widely available, although injections were rare. It was insulin, discovered in 1921 and had to be injected into the bloodstream, that really created the market for hypodermic needles. The modern needle hasn’t changed substantially since, although there is now a wide range of sizes and tip designs to suit every application. As well as a wide variety of needle diameters and lengths, there are numerous needle tip styles, such as single or multi-bevel facet, reverse bevel, spoon point, pencil point, diamond point, trocar, and then the ‘non-coring’ designs such as the Huber point needle.
But of chief concern to most of us getting an injection, apart from obligatory sterility and cleanliness, is: “how much is this going to hurt”? And for some, the pain associated with being pierced by a needle is a daily trauma, whether they are injecting themselves, or a dependent such as an understandably unwilling, uncooperative and distressed child.
One route to ridding us of needle pain is to remove the requirement for a needle entirely and use a different delivery mechanism such as pulmonary, oral or nasal delivery. However, for many drugs the alternate routes of administration are not an option and (of course) getting rid of the needle doesn’t necessarily remove the pain — needle-free injections are not known for being gentle.
So, assuming we are stuck with the needle, how can we reduce the pain? It has been shown that lower insertion forces reduce the likelihood of pain 2, 3, so that would be a good place to start.
Understanding needle force
The force on a needle consists of three elements — the puncture force (the force required to initially puncture the skin), the cutting force acting on the tip of the needle, and the friction force acting on the shaft of the needle. After the puncture event, as the needle is inserted, both the cutting and friction forces are in play, and when the needle is retracted only the frictional force is felt.
As the needle is pushed into the skin, the skin initially moves with the tip of the needle without being penetrated. The further the skin is depressed the higher the force it exerts back on the needle tip, until that force is high enough for the needle to puncture the skin (the puncture force). The puncturing can be described by fracture-mechanics, with a crack being formed in the skin, and the shape of that crack has been shown to depend upon the shape of the tip of the needle4. For example, a sharp bevel or conical needle forms a planar crack, a diamond tip forms a star-shaped crack, and a blunt or very large bevel angle tip forms a ring crack (like a hole-punch).
The tip insertion phase follows, when the crack in the skin is enlarged, the sharp edges of the tip wedging the cut open. The crack can grow gradually, following a stable ‘cutting’ mode, or can be sudden and unstable — a ‘rupture’, depending on the type of tissue and its properties and how much tension has been built up. As the tip goes deeper and wedges the tissue open wider, the force to push the needle in increases.
As auto-injectors and pen-injectors become more prevalent, and with the potential control offered by the electro-mechanical injector, we may be able to seize some opportunities for pain reduction.
After the tip is fully inserted, we are into the third phase as the shaft enters the skin. The needle tip continues cutting as it moves deeper but no longer widening the hole, so the force required to cut remains constant. However, as more needle is inserted the friction between the tissue and the shaft increases (as there is more shaft-tissue contact).
But how does the design of the needle effect these forces? In his comprehensive literature analysis of studies investigating needle-tissue interaction, D.J. van Gerwen noted that, although many studies do present insertion force data, dedicated experiments with true relevance and with statistically powerful results are actually thin on the ground5. But there are some good indications as to what is going on and what factors might affect the insertion force.
Two design factors clearly have an effect: the shape of the tip (multi-faceted bevel tips with shallow bevel angles exhibit the lowest insertion forces), and the diameter of the needle (smaller results in less force).
This would indicate that for minimal pain, the tip design must be right and the needle as small as possible. The prevalence of very fine insulin needles, and the vast research efforts dedicated to microneedles and microneedle arrays (fine, short, and reported to be practically painless) are testament to this approach.
However, not everything can be delivered with a tiny needle. Rapid delivery of large volumes requires large needles, and intramuscular delivery requires needles of sufficient length, strength and therefore size.
Enter the porcupine…
But there may still be room in needle development for pain reduction, other than just making the needles smaller. And like all great engineering clichés, we can look to nature for inspiration…
It has long been known that porcupine quills are difficult to get out once they have been put in. But what researchers at Harvard and MIT discovered in 2012 was that the quills of the North American porcupine go in much more easily than they should6. The reason for this is that, unlike their African cousins, hedgehogs or echidnas, which all have smooth quills, North American porcupines have microscopic backward-facing barbs running along their quills. The researchers found that the barbed quills required 54% less penetration force than equivalent barbless quills, and 60% less work to penetrate muscle tissue than the equivalent sized hypodermic needle. They also found that the barbed quills caused less tissue damage than barbless quills. Taking things one step further, the researchers fabricated a prototype hypodermic needle with microscopic barbs, and found that it had a penetration force 80% less than a barbless equivalent.
Their explanation for this effect was that the barbs acted in the same way as the serrations on a knife, providing stress concentrations near the barbs which cause the tissue to fail locally,thereby reducing the need to deform the entire circumference of tissue surrounding the quill, and consequently reducing the penetration force. This would align well with previous studies that found that the increased number of cutting edges found on a multi-facetted bevelled hypodermic needle reduced the penetration force when compared to a single-facet bevelled needle.
Vibrating needles during insertion leads to reductions in the puncture and friction forces (and subsequently pain) due, in part, to the viscoelastic properties of tissue. The gentlesharp system has been designed for use with animals and they claim a force reduction into cadaver rat-tails of up to 72.6%.
Reduced penetration force and reduced tissue damage should mean a less painful insertion. There is, unfortunately, a downside. As one might expect, the force to pull out the barbed quills was about four times higher than for a barbless quill. There could be uses for this in medical applications where tissue adhesion is desirable, such as in a drug-delivery patch featuring an array of needles that you want to keep in place, or in a cannula which, once in, you don’t want easily moved. However, for a standard injection you would want to be able to remove the needle as easily as possible. The researchers found that it was the flexibility of the barbs on the quills of the porcupine that provided the majority of the grip — as the quill was pulled out, the barbs would flex outward, thus increasing the apparent diameter, increasing frictional resistance and promoting tissue interlocking. However, their polyurethane quill mimics had barbs that could not flex, and in tests in skin they found the pull-out force for the mimic was almost a third of that for a natural quill. Unfortunately, this would still make the pull-out force significantly higher than for a standard hypodermic needle.
Improved needle control for pain reduction
But if we can’t reduce the pain by redesigning the needle, there may be another approach: control the way we insert the needle. As auto-injectors and pen-injectors become more prevalent, and with the potential control offered by the electro-mechanical injector, we may be able to seize some opportunities for pain reduction.
One method is the oscillating needle. Actuated Medical’s GentleSharp blood sampling system provides low frequency axial ‘micro-oscillations’ to the needle tip, achieving peak velocities of greater than 200mm/s. It is based on research that has indicated that vibrating needles during insertion leads to reductions in the puncture and friction forces (and subsequently pain), due in part to the viscoelastic properties of tissue. The GentleSharp system has been designed for use with animals, and they claim a force reduction into cadaver rat-tails of up to 72.6% and significant reduction in stress and behavioural response in a rat model.
As well as the oscillating needle creating a lower insertion force, GentleSharp also describe the potential anesthetising effect of vibrations as explained by the highly influential Gate Control Theory, an effect that other device manufacturers are also keen to exploit. First proposed in 1965 by Melzack and Wall, this theory asserts that a non-painful stimulation applied simultaneously to a painful stimulation can prevent the pain signal from traveling to the central nervous system. In other words the non-painful input closes the gate to the painful input.
Another route to reducing the needle insertion force, and so reduce the main, may be for an injection device to actively rotate the needle. In tests with animal tissues, rotating the needle as it is inserted appears to reduce the required insertion force4.
The DentalVibe and VibraJect devices, both intended for dental use, are based on the Gate Control Theory. Designed for use when administering injections in the mouth, the DentalVibe’s soft prongs vibrate while held next to the injection site just prior to (and during) the injection, the vibrations ‘blocking’ the pain signals. The distributors claim that ‘most patients feel nothing’. The VibraJect is a vibrating device which attaches directly to the dental syringe, sending its vibrations down the needle. The ‘Painless Vibrating Retractor’ from Practicon, also for use by dentists, is designed to work in the same way.
The effectiveness of vibrating injection devices for pain reduction has been disputed7. However, a study presented at the Anesthesiology™ 2014 annual meeting found that the perception of pain was significantly reduced when a specific amount of pressure and vibration was applied prior to a simulated needle stick, and that the application of heat also had a small but insignificant benefit8. The authors of the study explain that the pain-reduction effect is likely due to distraction as well as the Gate Control Theory.
Another route to reducing the needle insertion force, and so reduce the pain, may be for an injection device to actively rotate the needle. In tests with animal tissues, rotating the needle as it is inserted appears to reduce the required insertion force4. Pulling it out is a different story: there is a phenomenon in acupuncture called ‘needle grasp’, where it feels like the needle has been gripped by the skin. A study found that, in human skin, rotating the acupuncture needle before pulling it out could actually increase the pull-out force by up to 150%9. So, any device that rotates the needle on the way in should probably keep it still on the way out.
We are probably limited as to how much we can reduce the pain of injection by looking at the needle alone, but as devices that control how the needle is inserted become more common, and particularly with electro-mechanical devices, there could be opportunities to transform how we feel about injections. Until then, distract yourself from your injection by thinking about drunken dogs and bald porcupines.
References
1. Norn S, Kruse PR, Kruse E (2006) On the history of injection, Dan Medicinhist Arbog. 2006;34:104 – 13
2. Egekvist, H., Bjerring, P., Arendt-Nielsen., L., Pain and mechanical injury of human skin following needle insertions. European Journal of Pain 3(1), 41 – 49 (1999)
3. Egekvist, H., Bjerring, P., Arendt-Nielsen, L., Regional variations in pain to controlled mechanical skin traumas from automatic needle insertions and relations to ultrasonography. Skin Research and Technology 247 – 5 (1999)
4. Shergold, O.A., Fleck, N.A., Experimental investigation into the deep penetration of soft solids by sharp and blunt punches, with application to the piercing of skin. Journal of Biomechanical Engineering, 127(5), 838 – 848 (2005)
5. van Gerwen, D.J., Dankelman, J., van den Dobbelsteen, J.J., Needle-tissue interaction forces — a survey of experimental data. Medical Engineering and Physics 34(6), 665 – 680 (2012)
6. Cho et al, Microstructured barbs on the North American porcupine quill enable easy tissue penetration and difficult removal. Proceedings of the National Academy of Sciences 109(52), 21289 – 21294 (2012)
7. Saijo, M., Ito, E., Ichinohe, T., Kaneko, Y., Lack of pain reduction by a vibrating local anesthetic attachment: A pilot study. Anesthesia Progress 52, 62–64 (2005)
8. American Society of Anesthesiologists (ASA), An end to needle phobia: Device could make painless injections possible. ScienceDaily, 13 October 2014
9. Langevin, H.M., Churchill, D.L., Fox, J.R., Badger, G.J., Garra, B.S., Krag, M.H, Biomechanical response to acupuncture needling in humans. Journal of Applied Physiology 91, 2471 – 2478 (2001)
