Keywords
bladder pain - ilioinguinal - iliohypogastric
Interstitial cystitis (IC)/bladder pain syndrome (BPS) is characterized by lower urinary
tract symptoms along with pain, discomfort, or pressure perceived in the urinary bladder,
lasting longer than 6 weeks in the absence of infection or other identifiable cause.[1] Like other chronic pain disorders, IC/BPS remains a diagnosis of exclusion, with
no known single cause, and no accepted universal treatment, severely diminished psychosocial
functioning, and poor quality of life in black, Hispanic, and white men and women.[1]
[2]
[3]
[4] A review of bladder neurophysiology, emphasizing afferent innervation, and a discussion
of clinical observations related to referred pain can lead to a hypothesis for a microsurgical
intervention in BPS.
To understand the neurophysiologic basis of bladder pain, it is important to recall
that the bladder fills under normal circumstances with low-intravesical pressure (<
10 cm H2O). With bladder filling, the bladder's lamina propria thins and the detrusor muscle's
smooth muscle bundles reorganize from a top-to-bottom arrangement to a side-to-side
configuration[5]. Reorganization of the smooth muscle bundles is dependent on the activity of afferent
(sensory) A δ and C-nerve fibers,[5] and parasympathetic, postganglionic, efferent (motor), cholinergic stimulation from
the S2–S4 innervation.[6]
[7] Immunohistochemical studies localize the sensory fibers within the detrusor muscle
wall,[8] with unmyelinated C fibers extending into the urothelium, where they can be stimulated
by bladder inflammatory molecules and changes in acidity,[9] while the efferent fibers pass from the splanchnic nerves into the pelvic plexus
(inferior hypogastric plexus) and then into the bladder itself ([Fig. 1]).
Fig. 1 Illustration of three separate contributions to the bladder innervation, thoracolumbar,
sacral visceral, and sacral somatic, each of which contains both afferent and efferent
fibers. For the referred pain pathway, the thoracolumbar region (T12–L2) contains
the visceral afferent (dark green) input from stretch receptors in the bladder/detrusor
muscle wall. These participate in spinal reflex for bladder filling. Once a certain
bladder volume has been reached, the intensity of neural impulses peaks, and this
perception passes to the conscious level to permit voiding. It is hypothesized, here,
that the somatic afferent input from the iliohypogastric and Ilioinguinal (and perhaps
genitofemoral) nerves (dark purple) into the T12–L2 dorsal spinal cord can be misinterpreted
as arising from the visceral afferents from this same level, causing bladder pain
syndrome.
Despite this parasympathetic stimulation, the detrusor muscle does not contract, because
it is inhibited by nor-adrenergic stimulation from the T12–L2 sympathetic, postganglionic,
efferent (motor) innervation. However, with progressive bladder filling, the neural
circuit switches from inhibition to contraction of the detrusor muscle, which is initiated
by an increase in the conduction velocity of the afferent (sensory) fibers, transmitted
by visceral afferent, stretch fibers, into the T12–L2 (thoracolumbar) region. When
the sympathetic efferent inhibitory stimulation stops, the detrusor muscle contracts,
initiating micturition. As part of this reflex, the parasympathetic efferent input
to the internal and external sphincter is released to permit urine to flow. Voluntary
“over-ride” of this reflex is accomplished through the somatic efferent (motor) activity
of the pudendal (also S2–S4) nerve ([Fig. 1]).[10]
[11]
[12]
In 1994, a patient with 2 years of left lower quadrant abdominal and pelvic pain was
reported with onset of symptoms following an elective abdominoplasty.[13] At reoperation, she was found to have a muscle plication suture about the left iliohypogastric
(IH) nerve. Resection of this IH neuroma gave lasting relief of her left lower quadrant
and pelvic pain symptoms. Bladder pain, however, was not specifically reported. In
2011, Dellon described the referred pain of ilioinguinal (II) and IH neuromas to the
bladder, since the sympathetic innervation of the bladder had a similar origination,
that is, thoracolumbar sympathetic outflow to the bladder; both the sympathetic outflow
to the bladder and the II and IH arise from the same spinal segments, T12–L2.[14]
In this paper, we report two patients with IC/BPS who had their symptoms relieved
after resection of the IL and IH nerves. These clinical observations suggest that
the IC/BPS can be, in fact, a referred pain, a pain not originating from within the
bladder itself. The concept of referred pain as a source of IC/BPS has not been hypothesized
previously.
The commonly accepted referred pain “syndromes” are listed in [Table 1] along with their proposed neurophysiologic mechanisms. Referred to pain, as used
here, is the best understood in terms used by Doran in 1967,[15] “The physiologic mechanism of referred pain depends on nothing more complex than the
termination of pain afferents from the viscera, the deep somatic structures, and the
skin, on a common pool of connector neurons in the same segment of the spinal cord.
This theory only requires the basic physiological process of summation to make it
explain the observed clinical facts. The exact site to which … a pain is referred
is almost certainly finally determined by the higher centres of the brain.” Here, we propose the concept of referred pain from injury to the II and IH which
are somatic, afferent (cutaneous and sensory) branches of the T12 through L2 intercostal
branches, and possibly from injury to the genitofemoral nerve (GF), causing referred
pain interpreted as IC/BPS cortically. We propose an interaction with the known T12–L2
input from the bladder, the visceral afferents and, perhaps, the efferent sympathetic,
as the neurophysiologic mechanism of this IC/BPS referred pain.
Table 1
Examples of referred pain
|
Pain originates at
|
Pain referred to
|
Proposed referral Mechanism
|
|
Heart (myocardium)
|
Left arm
|
Vagus afferents link to C5–T1
|
|
Diaphragm/pleura
|
Shoulder/back
|
C3–C6 (phrenic n.) to intercostals
|
|
Rotator cuff
|
Deltoid/shoulder
|
C5–C6 motor/sensory
|
|
Hypopharynx
|
Middle ear
|
IX and X cranial nerve
|
|
Hard palate
|
Frontal sinus “brain freeze”
|
Trigeminal nerve to sphenopalatine ganglion
|
|
Thoracolumbar dorsal facets
|
Low back, thigh, groin
|
Dorsal ramus/ventral ramus, thoracolumbar region
|
|
Ilioinguinal and Iliohypogastric and genitofemoral
|
Bladder
|
T12–L2 somatic and visceral efferents
|
Methods
A review of the senior author's (A.L.D.) experience with groin pain patients from
1994 through the present was undertaken to identify patients with bladder pain. A
literature review of the study of bladder innervation and a review of the history
of bladder denervation for IC/BPS was done searching for evidence that can be used
to explain “T12–L2 referred bladder pain” hypothesis.
Results
The review of bladder innervation confirmed that there are three distinct sources
as illustrated in [Fig. 1]. The pudendal nerve, from the sacral nerve roots S2–s4 contains sensory input from
the rectum, perineum, urethra, scrotum/labia, and penis/clitoris which is perceived
in the sensory cortex, and motor output to urinary and bowel sphincters which is under
voluntary control. The parasympathetic innervation of the bladder also comes from
the sacral nerve roots, S2–S4, and is “involuntary,” autonomic motor supplying primarily
the detrusor muscle of the bladder, while at the same time conveying visceral afferents,
whose sensory impulses do not reach the cortex but rather are related to spinal reflexes.
In contrast, the thoracolumbar (T12, L1, and L2) region provides somatic afferents
from the groin and suprapubic skin whose impulses are perceived in the sensory cortex.
These cutaneous nerves are the II and IH nerves, and most often arise from T12 and
L1. The GF nerve originates from L1 and L2, and most typically has its sensory input
interpreted as testicular pain or mons pubis/labial pain, from its genital component,
while the perception of input from the femoral component is most often probably disregarded.
There is, however, a great variation in the skin territories innervated by II, IH,
and GF, with significant overlap patterns.[16] In patients where the femoral component of the GF nerve innervates the usual II
territory, the GF input may participate in the “T12–L2 referred bladder pain” mechanism.
With regard to bladder pain, signals arise from the visceral afferent component of
what is traditionally just considered as the “sympathetic outflow to the pelvis.”
It is true that visceral efferent, preganglionic, nerve fibers leave T12–L2 to synapse
within the hypogastric plexus leaving as postganglionic fibers to the pelvic structures,
including the bladder. But along this same pathway travel afferent fibers whose stretch
receptors lie in the bladder wall adjacent to the detrusor muscle, sending information
about bladder volume. When these afferent impulses reach the T12–L2 level, and synapse
in the dorsal horn, they permit stimulation that initiates a reflex that affects the
sympathetic discharge such that its inhibition of the detrusor muscle stops, initiating
bladder contraction. Some of this input also reaches the cortex allowing us to be
aware of the need to urinate. The neurophysiology is such that nociceptive input from
the injured II, IH, or sometimes GF nerve, can enter the dorsal horn of the thoracolumbar
region and be interpreted as impulses coming from the visceral afferents at that same
spinal level. These inputs summate, creating “T12–L2 referred bladder pain.”
Review of the senior author's patients, including those previously published,[17] identified just two patients in whom there was a clear complaint of IC/BPS. These
two patients and their surgical responses to resecting the II and IH are described
below:
Case 1
A 66-year-old man had a robotic prostatectomy in 2010. He awoke from surgery with
the perception that “glass shards” were sticking into his bladder. Neuropathic pain
medication was not helpful. Imaging studies showed no tumor recurrence and his PSA
remained at zero. His preoperative O'Leary–Sant voiding pain indices were 14 and 12,
and his pelvic pain and urgency/frequency scale was 17 + 11 = 28. His physical examination
demonstrated pain over the right lower quadrant portal, related to the II and IH nerves,
while the left side had no tenderness. At surgery, December 2, 2012, the right II
and IH nerves were divided at the level of the anterior iliac crest ([Fig. 2]), and the proximal ends of these nerves placed into the preperitoneal space. His
bladder pain was completely relieved. Five years postoperative his is O'Leary–Sant
voiding pain indices improved to 5 and 3, and his Pelvic pain and urgency/frequency
scale improved to 5 + 3 = 8. His last follow-up report was in November of 2018, 59
months after surgery. He remained without bladder pain or urinary symptoms.
Fig. 2 Abdominal wall of patient demonstrating incision medial to the anterior iliac crest,
with the excised iliohypogastric (IH) and ilioinguinal (II) nerves lying next to the
incision.
Case 2
A 16-year-old boy sustained blunt trauma to the right lower quadrant during a football
game in June of 2014. His symptoms were primarily “bladder pain” associated with urinary
frequency and urgency but no dysuria. His urgency and frequency was almost hourly.
He had seen 20 physicians over the preceding 17 months, cystoscopy was normal, neuropathic
medications did not help, and a sacral “interstim” did not give relief. Imaging studies
were all normal. His physical examination demonstrated discrete pain over the II and
IH region with referred pain to his bladder ([Fig. 3]). Because he was tender in the right lower quadrant, local nerve block into this
area was done, and gave him few hours of relief. A nerve block at T12/L1 gave relief
of the urgency and frequency for 6 hours. On November 5, 15, he had the right II and
IH nerves resected ([Fig. 4]). On follow-up, May 30, 18, 30 months after surgery, he remained without bladder
symptoms and was playing varsity soccer in high school.
Fig. 3 Case 2, demonstrating asterisk (*) at the site of trigger spot with pain referred to the bladder. The blue line is
the border to be prepared for surgery.
Fig. 4 Case 2 illustrating surgical approach to resecting the iliohypogastric (IH) and ilioinguinal
(II) nerves. (A) The white edge of the incised external oblique fascia is retracted to show the ilioinguinal
nerve lying upon the internal oblique muscle adjacent to the white inguinal ligament.
(B) The II nerve is shown on a retractor. (C) With the external oblique fascia retracted, the IH nerve is noted on the internal
oblique muscle more cephalad, near to the internal oblique fascia. (D) The IH nerve is grasped in a clamp.
Discussion
This is the first report of relief of IC/BPS by resecting one or more peripheral cutaneous
nerves. The weakness of this report is that it is based upon just two retrospectively
observed patients. However, the observations made permit expression of a hypothesis
of referred pain from somatic afferents, the II and IH nerves, and possibly GF, arising
from T12–L2, giving rise to IC/BPS by virtue of a similar origin from the thoracolumbar
spine as the visceral afferents to the bladder that travel with the sympathetic nerves.
Anderson and Langley, in a series of papers, in the late 19th century, had studied
innervation of pelvic organs. They reported that the hypogastric nerves contained
10% afferent fibers, and the pelvic visceral (splanchnic) nerves contained 33% afferent
fibers.[18] Thus, both the “sympathetic” and the “parasympathetic” outflow contain both visceral
afferents and visceral efferent nerve fibers. Today, these afferents are usually not
further discussed, with emphasis being placed on the motor function of these autonomic
nerves related to the detrusor muscle and the internal and external urinary sphincter
muscles. Here, we emphasize the importance of BPS as being transmitted primarily through
the thoracolumbar visceral afferents.
There have been direct attempts to relieve IC/BPS by dividing the presacral sympathetic
innervation. It is our view that these approaches did not simply consider that resection
of the sympathetic nerves or their plexus would also divide the accompanying visceral
afferents. For example, in his observations, made at surgery in patients having simultaneous
cystoscopy and stimulation/division of the presacral plexus, James Learmonth, a Neurosurgeon
then at the Mayo Clinic, noted “in one case, the patient stated that handling the presacral nerve with forceps was
attended by a crushing pain in the bladder.”
[11] Learmonth also noted that while division of the presacral nerve relieved bladder
pain, it has had little if any effect on urethral irritation.[11] (Our urethral sensory impulses travel with the pudendal, somatic afferents.)We might
ask if any of the patients that Learmonth reported as having been treated for bladder
pain might have benefitted from division of the II and IH nerves instead of having
a presacral neurectomy, which requires a challenging retroperitoneal dissection. One
of Learmonth's groups of patients did not have pain but had neurogenic bladder spasms
related to spinal cord injury, and these patients had relief by presacral sympathectomy.
Of his 11 patients treated for “vesicle pain,” one had bladder carcinoma, while the
others had a diagnosis of “interstitial cystitis” or “posterior urethritis.” None
of this group with, what we would today call IC/BPS, was reported to have had previous
abdominal wall surgery or trauma, so that most likely resection or nerve block of
the II and IH nerves would not have helped Learmonth's patients.
Learmonth was not the first to attempt bladder denervation. He reported that Piri,
in “Europe,” did the first presacral sympathectomy.[19] The translation of Piri's paper is “Clinical Contributions to the Surgery of the
Autonomic Nervous System IV. The Cure of Tuberculous Cystitis” (translated by Nicoletta
Ghisas, PhD) Learmonth may be considered to be the “first peripheral nerve surgeon,”
having done the first carpal decompression (1933) and the first submuscular ulnar
nerve transposition (1942).[20]
In extensive dissection, and electrical stimulation and recording of the canine bladder,
in 1937, Talaat reported that “the main function of the afferent nerve fibers in the
hypogastric (nerve) is to carry painful impulses.”[21] Talaat also noted that the “pudic nerve,” the pudendal nerve, when stimulated by
saline flowing in the urethra, gave an electrical response, but did not do so with
bladder distention. Learmonth observed directly in humans that stimulation of the
hypogastric plexus evoked perception of bladder pain.[10]
[11]
The next published attempt to learn more about bladder denervation was reported in
1938,[22] and attempted to learn why Learmonth's observed that some patients did not improve,
and some patients improved only briefly. Scott and Schroeder reported 11 patients
with bladder pain, primarily due to tuberculous disease, but in three patients from
unknown cause or interstitial cystitis.[22] They found additional branches arising from the inferior mesenteric plexus, and
some more laterally from the hypogastric plexus, so that if the surgical denervation
took this more widespread dissection approach in the retroperitoneum, a long-term
relief of bladder pain could be obtained.
Inclusion of the GF (L1–L2) nerve in this hypothesis seems warranted because patients
with IC/BPS report pain in the “genitals,”[23] patients with IC/BPS have segmental hyperalgesia in the T11 dermatome (T12–L2 were
not tested),[24] and the high percentage of women with “abdominal wall pain” associated with pelvic
pain.[25] To determine whether this inclusion is warranted, patients whose main complaint
is testicular or mons pubis/labial pain would need to be queried on whether they also
have symptoms consistent with IC/BPS and then have appropriate level spinal nerve
blocks to determine their outcome on the IC/BPS symptoms.
In more recent work, elimination of vagus afferents was shown not to affect the afferent
impulses to the thoracolumbar outflow track in mice, and the stretch receptors were
demonstrated, by immunohistological staining of (calcitonin gene-related peptide)
receptor, to be located in the detrusor muscle.[25]
[26]
[27] We may conclude from this that sensory input from the bladder reaches the thoracolumbar
dorsal root entry zone, where spinal reflexes result, and then that input is routed
up the brainstem to the conscious level for cortical interpretation. In the present
hypothesis, we conclude that the somatic input to this thoracolumbar spine from the
II, IH (and possibly from the GF) nerves evokes that same spinal response and cortical
interpretation.
Conclusion
Injury to cutaneous nerves of the lower abdominal wall, such as the II and IH nerves,
generate somatic afferent neural impulses that enter the thoracolumbar spine, interact
with visceral afferents from the bladder that travel along with the sympathetic efferent
fibers from that same T12–L2 region. These afferent inputs summate to be interpreted
(misinterpreted) as IC/BPS. This referred pain can be identified by appropriate nerve
block, and the IC/BPS symptoms relieve by microsurgical resection of the neuromas
of the II and IH nerves.
