While it is impossible to say with certainty, it is likely that this case represented a case of local anesthetic resistance. Traditionally, this has not been a topic that has garnered much attention. Reasons for this include rarity and the physician's attributing failure of block to technical failure or a defective local anesthetic solution. However, there is some increased recognition of this in the literature.
Yesterday, I received a question from a patient about this issue. The patient described a long history of receiving numbing medication which did not work. The most recent experience was with a podiatrist who attempted multiple times to inject around the nerves serving the foot only to finally give up.
To understand the possible causes of local anesthetic resistance it is helpful to review briefly what we understand regarding the mechanism of local anesthetics. For a fantastic review of local anesthetics mechanisms of action please see a paper by A. Scholz from which I borrow heavily here .
In vertebrates, local anesthetics (LA) are able to bind to voltage gated sodium channels (NAv) which are comprised of an alpha subunit and two beta subunits. The alpha subunit spans the cell membrane and forms a pore through which Na+ can flow upon depolarization. Importantly, it is known that mutations of the proteins that make up the channels result in several diseases. Since NAv channels are found on muscle, brain, peripheral nerve and heart cells, mutations in these proteins can effect all of these systems. An example are the isoforms of the NAv (known as Nav 1.5) located on cardiac muscle that lead to syndromes such as Long QT or Brugada. Furthermore, in animal models it has been shown that certain Nav isoforms proliferate in chronic pain. Thus, logic leads us to conclude that certainly mutations in the Nav isoforms that subserve the peripheral nerves and dorsal root ganglion (DRG) [include Na 1.6, 1.7, 1.8, and 1.9] would lead to resistance to LAs in some individuals.
The Nav channel exists in three states, resting (ready to fire), open (after cell has been depolarized) and inactivated. It has been demonstrated that Nav channels in the resting conformation are not susceptible to the effects of LAs. In effect, in the resting state, the pore created by the alpha unit is shut by a gate of sorts which is sensitive to the voltage across the cell membrane (thus the name voltage 'gated'). Therefore, LAs cannot readily get into a cell or into the pore near the inside of the cell when access is denied by a closed gate. However, when the cell is depolarized by some stimulus (i.e. pain), the gates open, Na+ flow in (and with them LAs), and not LAs can bind to the receptor and cause another gate to close off the pore not allowing further entrance of Na+ into the cell. So, LAs have two ways into the cell, directly through the pore created by the alpha subunit, or by diffusing through the cell membrane. Since the pore is often closed, much of the LAs that cause blockade must arrive through diffusion through the cell membrane. This explains why more lipophilic LAs have are more potent (more molecules arrive at the site of action). However, only noncharged LAs can diffuse passively through the membrane, and LAs tend to become charged (ionized) as the pH decreases (they are weak bases). Therefore, in acidic conditions, LAs become charged and do not have have the capacity to reach the receptor located deep inside the alpha subunit pore. However, if the the pore can be opened and held open, LAs that are charged, now are much more effective as it only the charged form of the LA is capable of binding the receptor and causing inhibition. Therefore, there are two clinical scenarios that affect LA effectiveness: 1) increased firing of neurons increase rate of blockade as the opening of alpha subunit pores allows charged LA molecules to arrive rapidly at the receptor and shut down the pore, and 2) increasing acidity can decrease rate of diffusion (or more basic can increase rate of diffusion) and thus block rate of LAs.
In rats, it has been shown that exchanging one amino acid on the Nav 1.2 channel (phenylalanine exchanged for alanine) can make the channel insensitive to use dependent block. This provides an excellent example then of mutations that can result in insensitivity to LAs in humans. More likely, is that some individuals have receptors (or pores) that make the LA less effective. Thus, by increasing the concentration at the site of action, one may be able to create a block. Investigators have shown that capsaicin can cause previously insensitive neurons to become sensitive. Furthermore, it has been demonstrated that Capsaicin applied to nerves can allow a lidocaine analogue name QX-314 access to the inside of the cell and thus cause blockade of sensorty neurons only. Under normal conditions, QX-314 does not cause blockade because it is permently charge (quarternary amide structure). But, after or with treatment with Capsaicin, QX-314 is able to gain access to the inside of the cell, and since it is permenently charged, it is very effective at binding to and inhibiting Nav channel.
Of course, clinical use of capsaicin is limited and much research needs to be done to see if this might serve as possible modality to aid in patients who have demonstrated a resistance to LA. Certainly, there likely to be multiple mutations that result in resistance, and pretreatment with capsaicin is likely to only address a few of them.