Introduction
Dorsal root ganglion (DRG) stimulation is a novel treatment modality for patients
suffering from chronic neuropathic pain. When compared to the traditional and broader
acting spinal cord stimulator (SCS) implants, DRG stimulation has been shown to be
more effective at treating chronic pain.1 However, the literature is mixed regarding
associated complications of DRG vs traditional SCS implantation. Some studies demonstrate
a decreased incidence of paresthesia in DRG stimulators versus SCS,1 while others
show an increased risk of developing new neurologic symptoms.2 The specific characterization
of these neurologic symptoms is also less clear. Herein, we present a case of a 49-year-old
female who developed neuropathic itching following a bilateral S4 DRG stimulator trial.
We include a literature review that demonstrates this approach as a novel and previously
unreported complication of a DRG stimulation trial. This project was deemed exempt
from the Mayo Clinic Arizona’s institutional review board as it acknowledged that
it did not meet the criteria for human subject research. The patient provided informed
consent for the case to be published.
Case Report
A 49-year-old female presented with persistent pain for 2 years consequent to falling
onto her lower back and buttocks. Following trigger point injections, epidural steroid
injections, sacroiliac joint injections, coccyx injections, and ganglion impar injections,
she was ultimately referred for a DRG stimulation trial. The patient underwent uncomplicated
placement of bilateral S3 DRG leads. Testing failed to provide coverage over her most
painful areas, and leads were immediately removed. Bilateral S4 leads were then placed
under fluoroscopic guidance, and testing during the procedure provided evidence of
excellent coverage. Overall, she tolerated the procedure well with no apparent complications.
Approximately 72 hours after the lead placement, she developed perianal and peri-vulvar
itching localized specifically to the S3 and S4 dermatomes. It initially was assumed
that the itching might be from the adhesive dressings, yet the itching persisted for
days after the leads were removed, was not associated with a topical rash and was
not present in the location of dressings. The patient reported excellent pain improvement
in response to the trial, although the itching persisted for weeks after the trial
leads were removed. She was treated with diphenhydramine to decrease the itching,
as she reported allergies to gabapentin and pregabalin. After 4 months, her itching
had reportedly improved substantially, although continued to be occasionally bothersome.
As she did not have a prior history of itching and did not initiate any new medications
that are known to cause itching, the new and focal itching was attributed to the DRG
trial leads.
Both itch and pain pathways in the nervous system are not completely understood. There
are many similarities between itch and pain transmission. Both pain and itching are
protective mechanisms for humans, pain to signal injury, and itching to signal any
foreign substance on the body (ie insects, parasites). A major difference between
pain and itch is that pain causes a withdrawal response while itch causes a scratch
response. Additionally, itch is typically confined solely to the skin surface, while
pain is not. Similarities include that both acute pain and itch can be protective
while chronic pain and itch are not. In both chronic pain and itch, there is spontaneous
firing in the nervous system as well as central sensitization. There are two main
types of itch: histaminergic and nonhistaminergic. C-fiber neurons transmit histamine-mediated
itch.3 It is unknown whether there are two independent neural pathways for itch and
pain or if they share common pathways. Many of the neurotransmitters involved in pain
transmission have also been demonstrated to be involved in the transmission of itch
sensation, including tumor necrosis factor, interleukin-1, interleukin-6, Substance
P, and prostaglandins.4 There are primarily two known neuropathic itch conditions
that arise from nerve irritation rather from a particular skin disorder: brachioradial
pruritus and notalgia paresthetica. Although the specific mechanism of brachioradial
pruritus is not fully understood, it is thought to represent a combination of both
cervical nerve irritation (C5-C8) and skin exposure to sunlight.5 Notalgia paresthetica
presents as itching in the upper thoracic dermatomes (T2-T6) and occasionally involves
associated pain. It is thought that nerve irritation causes this syndrome as well.
That afferent nerve irritation can cause itch supports the hypothesis that both pain
and itch share similar neural pathways. Another known similarity of pain and itch
is that activation of the mu-opioid receptors can cause itch. There is also a psychosocial
component to both itch and pain in that even thoughts of itch and pain can trigger
both responses.
Literature Review
We conducted a literature review by searching PubMed, dates ranging from 1986–2020,
with the key words “neuropathic itch DRG”, “neuropathic itch stimulator”, “DRG stimulator
itch”, “DRG simulation complication itch”, “DRG stimulator pruritus”, “spinal stimulator
itch”, OR “spinal stimulator pruritus”. A total of 123 results were reviewed, and
none was related to DRG or spine stimulator placement complications or their relation
to itch. A secondary search of “DRG stimulation complications” yielded 137 results,
of which 3 papers were reviewed for information concerning reported complications.
A pooled analysis by Huygen and colleagues found the most frequently reported complications
of DRG stimulation were infections (5.1%), lead fractures (5.9%), lead migration (5.9%),
temporary motor stimulation (4.7%), dural puncture (4.3%) and pain at IPG pocket site
(10.2%).6 There was no mention of itch or pruritus as a reported complication. A recent
retrospective analysis by Kretzschmar and colleagues determined that their complications
were consistent with those that Huygen et al had reported.7 Another recent study by
Horan and colleagues determined that the most common complications were defective
electrodes (39%), an inability to replace electrodes (21%), migrated electrode (15%),
electrode fragment left in patients (12%), nerve damage (9%) and infection (6%).8
Neither of the studies mention itch or pruritus as a possible complication.
Eldabe and colleagues conducted a literature review of complications of traditional
spinal cord and peripheral nerve stimulation and noted that hardware complications
were more common than biological complications.9 In addition, complications concerning
neurologic damage were related to major neurologic deficit (0.25%), limited motor
deficit (0.14%), autonomic changes (0.013%) and sensory deficit (0.10%). There was
no mention of complications related to itch or pruritus. A study by Sivanesan and
colleagues concluded that use of DRG stimulators may result in an increased risk of
developing new neurologic symptoms when compared to traditional spinal stimulators.2
However, there was a lack of the characterization of these symptoms, with no mention
of itch or pruritus as a complication. Given our literature review, we believe our
case is likely the first reported DRG stimulator trial resulting in neuropathic itch
as a complication.
Discussion
Our patient experienced new onset itching isolated to the S3 and S4 dermatomes 72
hours post-sacral DRG SCS trial. In the absence of another etiology for itching such
as skin irritation or new medications, the patient was diagnosed with neuropathic
itching as a complication of sacral DRG stimulator lead placement. Evidence suggests
that DRG stimulator placement is associated with an increased incidence of neurologic
side effects compared to traditional SCS. One proposed mechanism links causality between
new neurologic symptoms and spinal dural puncture secondary to the manipulation of
needle, guidewire and DRG lead required for lead placement.2 A second mechanism relates
the manipulation of various components at the neural foramen leading to nerve compression
or trauma. This may explain the increased incidence of neurologic symptoms in DRG
versus traditional SCS, which does not require manipulation within the fixed space
of the neural foramen. While the thoracic and lumbar DRGs are subpedicular in location,
the sacral DRG location differs in that it is either intracanalar or intraforaminal.10
At S3 and S4, specifically, one study noted that 100% of the DRGs were intracanalar,
or medial to the medial border of the pedicle in the sacrum.11 The relevance of anatomic
differences between the sacral DRGs compared to lumbar and thoracic DRG location in
regard to adverse effects are currently unclear, however.
Neuropathic itch is not as well studied as neuropathic pain, yet remains clinically
important and impactful to patients’ qualities of life. There are multiple etiologies
for neuropathic itch including nerve fiber compression and generalized fiber degeneration.
Nerve fiber compression typically causes itch that is localized to the dermatomal
distribution of the nerve, while generalized fiber degeneration can lead to either
generalized or localized itch. Our patient’s neuropathic itch was localized to the
S3 and S4 dermatomes, which is likely clinically consistent with the principle of
nerve compression. In addition, because DRG lead placement requires component manipulation
within the neuronal foramen, it is likely that our patient’s neuropathic itch was
secondary to nerve compression at the S3 and S4 foramen. Furthermore, the fact that
our patient’s neuropathy was characterized as “itching” rather than “pain” was intriguing.
This is a complicated topic with multiple theories attempting to explain the arising
sensation of itch versus pain. Some of these include spatial contrast, temporal pattern,
specificity theory and phenotypic switch of nociceptors.12 The spatial contrast theory
focuses on the pattern of nerve discharge creating a “mismatch signal” that produces
the sensation of itch. The temporal pattern focuses on the frequency of nerve discharge
while the specificity theory is concerned with neurons critical for itch, such as
GRP-releasing neurons. It is likely that some combination of all of these theories
contributes to the sensation of itch and its differentiation from pain.