A New “Denervation” Technique for Painful Arthritic Wrist

Abstract

Wrist denervation is, by the way, one of the most performed and long-lasting surgical technique for wrist arthritis. Despite many progresses in upper extremity joint arthroplasty, wrist arthritis remains difficult to treat specially in young patients and heavy manual workers. The aim of this technical article is to describe a new outpatient's procedure in which applying pulsed radio frequency on nerve structure of the wrist could achieve similar clinical results of a wrist denervation without surgical incision.

Nicolas Rüdinger (1832–1896) first described joint innervation that became the basis of later technique of surgical joint denervation. ¹ In 1862, John Hilton put forth Hilton's law which states that nerve crossing a joint innervates that joint. ²

A complete surgical denervation on an arthritic wrist was performed in 1959 by Albrecht Wilhelm on a 30 years old patient with scaphoid nonunion advanced collapse (SNAC) wrist. The procedure was significantly invasive with five surgical approaches for the denervation of 10 terminal sensory nerve fibers. ³

Although year by year since 1959 many authors have described numerous different denervation procedures for painful wrist arthritis, a definite technique is not yet been identified but mostly favorable results had been reported. ⁴

The concept of wrist denervation to address the symptomatic wrist arthritic pain is not new but its practical application has been modified over the past 50 years.

Despite the fact that total wrist denervation requires multiple incisions and some studies speculate that it may result in the loss of wrist neuromuscular stability, ^{5 6} partial wrist denervation is being routinely performed.

Dellon first described the concept of partial wrist denervation in 1985. ⁷ In 1998, Berger defined a denervation surgical technique that consists of a singular surgical approach on the dorsal wrist for a combined anterior interosseus nerve and posterior interosseous nerve neurectomy. ⁸

Wrist arthritis in young patients and heavy manual workers who failed or avoided nonoperative treatment is traditionally addressed through salvage procedures such as proximal row carpectomy and partial arthrodesis depending on patients' functional needs.

Total wrist arthroplasty is a motion preserving procedure but there are limitations concerning prosthesis longevity. Even if newer fourth-generation implants appear to be performing better, the risk of complication following wrist replacement is still very high.

Wrist denervation is a palliative surgery and actually is indicated for painful wrist osteoarthritis in patients with good mobility.

The indication is mainly based on disabling pain of the patient and his inability to work. That is the main reason why we think a different approach could be useful.

Pulsed Radio Frequency

Pulsed (PRF) consists of a large current density (estimated 2 × 104 A/m ² ) ⁹ delivers from the tip of an electrode. The theory of pulsed RF is that the tip of an electrode delivers a large current density, estimated as 2 × 104 A/m ² . ⁹ This current can be applied to a nerve, without heating it, and without creating a histological lesion, by delivering the current in very brief pulses. The recommended protocol involves delivering a current of 50,000 Hz in 20-millisecond pulses, at a frequency of 2 per second. By limiting the delivery of current in this manner, the relatively long pause between pulses allows any heat generated to dissipate, thereby preventing the development of any thermal lesion. Heat is further minimized by limiting the electrode tip temperature to less than 42°C. Meanwhile, the electrical current, and its purported therapeutic effect, is delivered to the nerve. As the greatest density of the electric field is near the tip of the electrode, the applied current is densest distal to the tip of the electrode. This rationale allows the electrode to be applied perpendicular to the target nerve.

Studies have explicitly examined the pathological effects of pulsed RF in laboratory animals. In one study, neither continuous RF nor pulsed RF, at 42°C, produced any lasting effects on a dorsal root ganglion (DRG). Both types of treatment produced edema at 2 days, which was resolved by 21 days; but the DRG cells remained structurally normal. Similar effects were observed when the same lesions were applied to a sciatic nerve. ¹⁰ In another study, no structural lesions were found on light microscopy, following application to a DRG of either a continuous RF current at 67°C or a pulsed RF current at 42°C. Electron microscopy, however, did show some changes. In the ganglia treated with continuous RF at 67°C, DRG neurons exhibited numerous, giant cytoplasmic vacuoles fused with each other, and enlarged endoplasmic reticulum cisterns; in some cells, there was loss of integrity of nuclear and neurolemma membranes. In the ganglia treated with pulsed RF at 42°C, enlargements of endoplasmic reticulum cisterns were observed, along with some vacuole groups, in DRG cells, but membranes were intact. Following either of the treatments, myelinated and unmyelinated nerve fibers remained normal in morphology. These morphology studies corroborated the inference from the physiology studies: that pulsed RF does not produce a lesion in the nerves treated.

The pulsed RF theory explicitly maintains that no lesion is created in the nerve. ⁹ The fact that no histological lesion (axonotmesis or neurotmesis) is created has been borne out by laboratory studies. A study that predated the concept of pulsed RF showed that applying a continuous RF current to a peripheral nerve, with a tip temperature of 40°C to 45°C, resulted in reversible conduction block in the nerve. ¹¹ Upon cessation of the current, conduction promptly reverted to normal. Brodkey et al demonstrated that the same effect was achieved by heating the nerve using water circulated through a coil around the nerve. ¹¹ Thus, heating a nerve to low temperatures (40–45°C) temporarily blocks conduction along the nerve, but the rapid recovery of function indicates that no physiologic lesion is produced. These experiments do not exclude a possible induced electrical effect of RF current, but the fact that heated water achieved the same effect strongly suggests that it is the low level of heat produced, not the current itself, which was responsible for the temporary conduction block. In a study using slices of hippocampus as the target tissue, ¹² two protocols of pulsed RF (one at 38°C and one at 42°C) and a 42°C continuous (“thermal”) RF current were applied for 120 seconds. The continuous current reduced excitatory postsynaptic potentials (EPSPs) to less than 50% of normal amplitude, for the duration of the experiment (25 minutes). The 38°C pulsed RF reduced EPSPs to 75% normal amplitude for 5 minutes after application. Thereafter, normal amplitudes recovered. The 42°C pulsed RF reduced EPSPs to 50% normal amplitude for 5 minutes. Thereafter, normal amplitudes recovered. Beyond 2,000 µm from the electrode, neither of the pulsed RF protocols produced any lesions in the tissue; neither did the continuous thermal protocol. Between 500 and 1,000 µm, tissue damage occurred with the thermal protocol but not with either pulsed protocols. Within 500 µm, all protocols produced tissue damage. These results show the expected effect of even a low temperature continuous RF thermal lesion. Tissues were coagulated to a distance slightly greater than one electrode-width from the surface of the electrode (1 mm). This coagulation was consistent with marked reduction in function of the affected tissues (EPSP > 50% reduced for at least 25 minutes). In contrast, both pulsed RF protocols produced only a minimal lesion immediately around the surface of the electrode (<0,5 mm). Although neural function was suppressed, the effect was only transient (5 minutes), which is consistent with no significant permanent lesion having been made. A third study examined the effects on cells in the dorsal horn of the rat spinal cord following pulsed RF application to the C6 DRG. ¹³ The C6 DRG was exposed to continuous RF or pulsed RF at 38°C. The animals were sacrificed 3 hours after exposure, and immunohistochemical assays for c-fos reactivity were performed. Animals treated with pulsed RF at 38°C exhibited increased expression of c-fos in lamina I and lamina II. These effects were not seen in animals treated with continuous RF at 38°C. These results indicate that pulsed RF activates sensory fibers in the DRG and the spinal neurons to which they relay. The clinical implications of this finding are not known. The duration of changes in dorsal horn c-fos is not known, as animals were sacrificed 3 hours after RF exposure. The fact that continuous RF did not produce changes in dorsal horn c-fos indicates that it is not electrode current itself but its delivery in pulses that is responsible for the effect. Somewhat contrary results were obtained in another study. ¹⁴ It examined the effects on dorsal horn cells of both continuous and pulsed RF applied to the C6 DRG compared with sham treatment. Both forms of RF application induced increased c-fos expression in the dorsal horn. This contradicts a specific effect attributable to the delivery of current in pulses. Collectively the results of these studies provide extremely limited insight into the potential physiological effects of pulsed RF. The study of Brodkey et al ¹¹ did not address the effects of pulsed RF, but it established a reference point. Heating a nerve temporarily blocks conduction along it. This is compatible with the effects observed by Cahana et al caused by a continuous 42°C RF lesion, but not pulsed RF at 38°C or 42°C. In contrast to continuous RF lesions, pulsed RF seems to have limited effects. It transiently suppresses, but does not abolish, EPSPs in tissue slices, ¹² and it also seems to activate a subset of central spinal cord neurons. ¹³ Specifically, however, pulsed RF does not produce a tissue lesion. Any therapeutic effect, therefore, would seem to be akin to a brief and mild electrical stimulation, perhaps not unlike the effects of a brief application of transcutaneous nerve stimulator or an implanted nerve stimulator. The findings that pulsed RF, and continuous RF for that matter, increase expression of c-fos do not provide an explanation for the effects of RF. Expression of c-fos is no more than a marker of increased cellular metabolic activity; it is not even specific for nociceptive pathways. It indicates only that cells are activated. It does not distinguish between inhibitory and excitatory activity. It is not evidence that patients will be relieved of their pain. For such reasons, an editorial ¹⁵ concluded that “basic scientific studies in the neurobiology of pain models and analgesic techniques are not a substitute for randomized controlled clinical trials, and studies such as that of Van Zundert et al. ¹⁵ do not justify using the technique clinically.” A revised theory has sought to convert the original, purely electrical model into a thermal one. ¹⁶ The theory proposes that, during each pulse, the electrode is heated temporarily, and that this heat is responsible for the therapeutic effect. An accompanying study, using finite-element modeling, explored the magnitude of this effect. It showed that the point of the electrode did, indeed, produce heat. However, the range of influence was limited. Heat was generated at 0.3 mm from the tip, but was proportional to the intensity of stimulation. Large increases in temperature occurred only at voltages well above those commonly used in practice. Meanwhile, the theory also still holds out that the electric field of pulsed RF might depolarize and disrupt nerve cell membranes.

In addition to the histological and ultrastructural axonal findings in PRF, and the animal studies demonstrating PRF effects, there are also convincing biochemical basis for PRF effects. Higuchi et al ¹³ demonstrated that pulsed but not continuous RF applied at 38°C to the rat cervical DRG resulted in increased c-fos immunoreactivity in the laminae I and II of the dorsal horn 3 hours after treatment. These effects were not seen in animals treated with continuous RF at 38°C. Although not specific for nociceptive pathways, the expression of c-fos is an indirect marker of neuronal activity as c-fos is often expressed when neurons fire action potentials. ^{17 18} Its presence indicates that nerve fibers have been activated by high electric fields, and that these changes are detectable up to the dorsal horn of the spinal cord. Lending further evidence to the definite biological effects of PRF, an upregulation of activating transcription factor-3 (ATF-3), another marker of “cellular stress,” was observed in the DRG neuronal bodies in animal models with PRF applied to the L4 DRG compared with sham-operated and L4 axonotomized controls. ¹⁹ In addition, Hagiwara et al ²⁰ more recently demonstrated that PRF may actually enhance the descending noradrenergic and serotonergic inhibitory pathways, which are intimately involved in the modulation of neuropathic pain. From the available evidence, PRF appears to have genuine biological effects in cell morphology, synaptic transmission, and pain signaling, which are likely to be temperature independent.

There had also been some anecdotal reports and retrospective studies on the intra-articular application of PRF. ²¹ Given the paucity of evidence for intra-articular PRF, we cannot even begin to imagine how this might work. The authors suggest that the current is actually deflected by the bony surfaces of the joint, forcing it to remain inside the joint space, and thus, resulting in a more localized effect. ²¹ There may, in fact, be a plausible explanation for this: Electric fields have demonstrated effects on immune modulation, as there are studies that show proinflammatory cytokines, such as interleukin (IL)-1b, tumor necrosis factor-α (TNF-α), and IL-6, are attenuated by electric fields. ²¹ Upregulation of adenosine A2A receptor density has also been observed in human neutrophils treated with generated electric fields, ²² and this appeared to be associated with inhibition of the catabolic cytokines, such as TNF-α, IL-6, and IL-8. ²³ Another hypothesis on the mode of action of intra-articular PRF is a possible cartilage-protective or regenerative mechanism. In vitro studies have demonstrated that chondrocyte proliferation and matrix synthesis were found to be significantly enhanced by electric field exposure. ^{24 25 26 27} Fini et al ²⁸ suggest that pulsed electric field delivery combines an anabolic effect on chondrocytes, a catabolic cytokine blockage, a stimulatory effect on anabolic cytokine production, and a counteraction of the inflammatory process in osteoarthritis. However, these effects are at the moment restricted to observations that will need to be reproduced in vivo in a more systematic manner. Future research may involve changing our focus from pain transmission and neural tissue effects, and broaden the evaluation of PRF to different cell lines and tissue types.

Technique Description

After Wilhelm pioneering anatomical work, in the past decade, wrist innervation has been widely described in his microscopic constituents inside intrinsic and extrinsic ligaments. ^{29 30}

It has been established that volar ligament has little or no innervation, on the contrary dorsal ligaments have abundant innervation and are consider sensory important ligaments. ³¹

On this anatomical basis, Hagert et al have described some nerve sparing dorsal and volar wrist approaches. ³²

Taking into consideration these anatomical landmarks, we develop our technique.

The procedure is conducted in an outpatient's service.

There is no need for preoperative blood tests, fasting, ECG, chest X-Ray, etc.

The benefits, risks, and alternative treatments are explained to the patient and informed consent is obtained. All patients are informed that this might not be a definitive procedure and surgery may become necessary later on.

The patient is placed in the sitting position with the elbow flexed and the forearm and hand resting comfortably palm down on a pillow or padded bedside table ( Fig. 1 ).

Fig. 1.

Patient placed in the sitting position with elbow flexed and the forearm and hand resting palm down on a pillow.

The skin overlying the radiocarpal joint is then prepped with antiseptic solution.

The cannula is placed into radiocarpal joint under ultrasound view ( Fig. 2 ). The Stylette is removed from the cannula and is replaced by the thermocouple probe. The operator initially attempts to seek the nerve by low-voltage stimulation at the frequency of 50 Hz; one seeks the strongest possible sensory stimulation at the lowest possible voltage. The way this is done, once the sensory nerve has been located, is by stimulating at a low frequency (2Hz). If no muscle twitch in the territory of the nerve is noted at twice the voltage strength necessary to achieve sensory stimulation, it can be safety assumed that there are no motor paths within 3 mm of the needle and that consequently, there is no risk of damage to any motor nerve.

Fig. 2.

Cannula placed into radiocarpal joint under in-plane ultrasound view.

The procedure is repeated into distal radioulnar joint under ultrasound view ( Fig. 3 ).

Fig. 3.

Cannula placed into distal radio-ulnar joint under out-of-plane ultrasound view.

The RF technique applies a maximum temperature of no greater than 42°C and utilizes the strong electric field generator by the passage of the RF current to achieve pain relief.

To apply an electric field to the tissues, without raising the tip temperature above 42°C to eliminate any possibility of a heat lesion being produced, the RF current can be applied in a pulsed fashion. The “silent” period between pulsed allows foe the dissipation of heat produced during the active cycle. This technique delivers a high generator output without raising the tip temperature above 42°C. ³³

The therapeutic cycle has a duration of 300 seconds.

At the end of cycle, a small dose of local anesthetic and steroid is injected under real-time ultrasound guidance to reduce postprocedure pain.

Clinical Case

M.L. is a 56-year-old patient who came to our department, when he was 50, for pain in his right wrist. We came up with a diagnosis of SNAC wrist ( Fig. 4 ) and patient was seeking treatment because he was not able to perform his heavy manual work since the right hand was is dominant one.

Fig. 4.

SNAC wrist in a 56-year-old patient.

After a period of physical therapy, the patient was informed about alternative treatments and chose partial arthrodesis because his main goal was to accomplish his job again.

We performed a capitolunate arthrodesis ( Fig. 5 ) and after 4 months he was able to resume his occupation.

Fig. 5.

Capito-lunate arthrodesis.

Five years later the patient returned with pain symptoms again and X-ray exam showed radiocarpal arthritis. Steroid injection in radiocarpal joint and physical therapy could not treat his pain who limited his daily activity.

The patient was in his last year of service before retirement and did not want a surgical solution for his problem.

Furthermore, treatment options were complicated by his postsurgical status.

Patient was referred to pain therapy for treatment.

After the evaluation from the pain specialist, an anesthetic injection with only 0.5% bupivacaine at the radiocarpal joint was performed under real-time ultrasound guidance with regression of pain.

The patient was, therefore, selected for a RF treatment.

Outcome and Follow-Up

We measured patient satisfaction after pain specialist's procedure with Disabilities of the Arm, Shoulder and Hand (QuickDASH) score and with numeric rating scale (NRS) at 3 weeks and 6 months

The patient had a significative improvement in QuickDASH score: 43,2 points during the first 3 weeks.

Our patient did not show an improvement in the range of movement but a remarkable increase on pain control.

The NRS pain scale has improved from 8 to 1 during the first 3 months after the treatment. Such an improvement allows the patient to accomplish their heavy manual work just a few days after the pulsed RF were applied.

However, these results seem to decline considerably at 6 months; the QuickDASH score measured was 9.1 points. The NRS pain scale at 6 months was improved of just 1 point.

The patient would repeat the same treatment again.

Discussion

The technique we presented is different from a denervation. It is a minimally invasive, outpatient procedure with palliative purpose in arthritic painful wrist.

It is based on the use of RF currents that act in the vicinity of nerves and the pathways of chronic pain, altering the functionality of some nerve fibers.

PRF maintains the temperature of the heating tip between 40 and 42°C during the procedure, allowing the neuromodulation of the dorsal roots without causing nerve damage. PRF seems to cause microscopic and intracellular damage such as mitochondrial edema and cytoskeleton, microtubule disorganization and microfilaments, myelin sheath rearrangement, due to the development of an electric field, rather than to the temperature rise near the DRG. ¹⁵

The exact mechanism of action of the PRF and its therapeutic effects is still under discussion. It is believed that microstructural changes in nerve tissues generated by the electric field are responsible for the blocking of pain transmission. ¹⁶ The stimulation of the dorsal root ganglion seems to reduce neuronal excitability with analgesic effect thanks to the inhibitory action on the generation and propagation of action potentials. ¹⁷ Several authors agree on the hypothesis that PRF can act on the transcription of various “pain genes” in the posterior horns and dorsal roots (e.g., increasing the expression of c-fos, activating transcription of ATF3, reducing the calcitonin-related gene peptide/CGRP) and acting selectively on small fibers Aδ and C. ^{18 19} Microscopy studies have shown ultrastructural damage in small-caliber fibers exposed to RF, with more marked on C-fibers ²⁰ . Ganglion PRF also showed an immunomodulatory action with reduced production of proinflammatory cytokines such as TNF and IL-1.The application of PRF on animal models has allowed to document an activation of the serotoninergic and noradrenergic descending antinociceptive system, as well as a significant modulation of microglial activity. ²¹ Finally, the hypothesis of neuromodulation resulting from synaptic plasticity mechanisms similar to those of long-term depression has also been brought into play. ²² Unfortunately, few randomized studies on the efficacy of PRF are still available and with conflicting results on chronic lumbosacral root pain. This could be due to the high heterogeneity of the disorders responsible for lumbosacral pain, the different criteria for inclusion, and exclusion of patients or the lack of guidelines on the application of PRF. Due to the complexity of the method and the pathophysiology of lumbosacral pain, it is necessary to develop new study protocols that therefore help clarify the real potential of RF.

The idea beyond the use of RF in the wrist arthritis is to modulate rather than remove, like in denervation technique, a nerve that transmits a pain message improving pain-free joint function.

We think our technique has several advantages, first of all it does not require any surgical incision and can be conducted in an outpatient's service. This allow us to reduce the number of complications and the cost of a surgical setting.

Second, the procedure we described do not denervate the joint but nearly show the same result on alleviating the pain, at least 3 months after the procedure. We think this is favorable for wrist neuromuscular stability and does not burn any bridges for further surgical treatments.

Third, the procedure is less invasive because more than using surgical incision can operatively act on the source of the pain, whatever is located radially, centrally or ulnar side on the patient's wrist. In other words, it acts directly on nerves that transmit a pain message improving pain-free motion of wrist joint.

If we look back to the history of joint denervation, we can clearly see that wrist and proximal interphalangeal joint in the hand are the only articulations where denervation is still considered an actual procedure for the treatment of painful arthritis.

As the technological advancement allows us to modulate with electric fields the pathway of pain transmission, we think this technology can be beneficially applied in the treatment of painful arthritic wrist. At least as long as a new generation of wrist arthroplasty will be developed.

Dealing only a single case report it is necessary to collect more cases to standardize the procedure.

Anyhow the procedure described could be another therapeutic option specially in patients who do not wish a radical surgical option or cannot, for medical rather than personal reason, deal with a surgical setting.

We think the only limitation of the technique comparing with partial or total wrist denervation could be the durability of the result.