Prolonged Sensory Block Using Ammonium Salts

Intracellular alkalization causes pain sensation through activation of TRPA1 in mice

“…Injection of ammonium salts into peripheral nerve induces a short-term increase in pain intensity resulting in prolonged pain relief, which might be explained by TRPA1 activation and desensitization (15,16), respectively, a phenomenon that is well documented in TRPV1. These previous studies suggest the possibility that TRPA1 is activated by high ammonia concentration and thereby detects changes in physiological conditions.…”

“…The intracellular pH increase by ammonium salts is thought to be induced by ammonia's rapid diffusion into the cell, where most of it combines with protons (14). Meanwhile, ammonium salts were introduced for the relief of nerve root pain and intercostal neuralgia (15,16), although pain intensity increased immediately after the injection of ammonium salts for approximately 30 minutes (16). Moreover, ammonia-induced intracellular alkalization was demonstrated with a microelectrode in barnacle muscle fiber and the squid axon (17,18).…”

Subcutaneous infiltration with ammonium sulphate 10% does not prolong the local anaesthetic duration of lidocaine in humans

“…First, it has been speculated that the possible neurolytic action of ammonium sulphate may be caused by reversible protein binding in the nerve membrane ( 15), thereby producing a local anaesthetic action on its own or by prolonging the effect of commonly used ester or amide caine local anaesthetics, such as procaine or mepivacaine. However, from older reports injection with ammonium sulphate was known to give rise to a burning pain and possible exacerbation of existing neuropathic pain lasting for about 30 min ( 12, 13), probably caused by the unavoidable hypertonic nature of the solution. From our own experience we knew that adding of local anaesthesia only would reduce but not totally eliminate the pain on injection.…”

“…Subcutaneous infiltration with the test medications was performed on marked similar 15×25 mm rectangular skin areas 20 cm proximal to the ankles on the medial surface of the right and left calf. Because injection of solutions containing ammonium sulphate may cause an intense stinging pain ( 12, 13) all subjects, 5 min prior to infiltration with the test medications, received subcutaneous infiltration with 3 ml of 1% lidocaine on either side in the test area. This was done in an attempt to eliminate any pain during the following injection of ammonium sulphate in order to preserve the blinding of the trial.…”

“…Ammonium sulphate is an agent which, in older papers since the 1940s ( 9–14), has been sporadically reported to provide prolonged pain relief after nerve blocks or infiltration, and to prolong the duration of action of ordinary local anaesthetics. Indeed, a recent paper investigated possible neurotoxicity of ammonium sulphate after intrafascicular nerve injection in an animal model ( 15), and found it to be as safe as bupivacaine.…”