Neuropathic Pain Resulting From Pelvic Masses

Cancer patients can expect to suffer pain, particularly in the advanced stages of the disease. Optimal pain control is an essential part of cancer management from the time of diagnosis, as pain can interfere with cancer therapy, limits patient function, and negatively impacts quality of life.

Pain can result from primary solid tumors of the pelvic organs and other pelvic tissues; from metastatic tumors; or from nodal conglomerates causing mass effect. Bony pelvic tumors may extend into the pelvic cavity. Tumors of neural structures arise in the pelvis. Pain may follow treatment of pelvic masses and other associated problems. Cancer patients may have painful conditions unrelated to their disease. Having a full understanding of the pathophysiology of pain and the ability to make a pain “diagnosis” are essential to effective pain management.

One of the more challenging aspects of cancer pain management is neuropathic pain, that is, the particular type of pain related to nervous system dysfunction. Neuropathic pain may be due to mass compression or traction of nerve structures, which in the pelvis includes irritation of a single nerve or multiple nerves, tumor infiltration of the lumbosacral plexus in the pelvic sidewall, or a presacral mass affecting the sacral plexus. Initially, non-neural tumors will cause inflammation of nerves and nociceptive nerve pain, conditions that if not addressed will, over time, progress to nerve damage and the deafferentation type of neuropathic pain. At this point in the process, pain is accompanied by neurologic deficits.

Pain can be felt by the patient at the site of tumor, or it may refer to another location in somatic referral patterns, or along nerve root patterns (radicular) or in a non-radicular pattern, or it may have combined features. A critical differential diagnosis for pelvic tumor–related neuropathic pain is compression of the conus medullaris of the spinal cord, resulting in pain and sensory loss in the saddle area (buttocks and perineum) but without lower-extremity symptoms or signs.

Neuropathic pelvic tumor–related pain may be associated with other types of pain, such as pain related to tumor infiltrating bones of the pelvis, aseptic necrosis of bone, shedding of coccyx fragments, radiation enteritis and proctitis, pelvic visceral distension, fluid accumulation (ascites), fistulae, and infections. The patient may also have neuropathic pain resulting from surgery, radiation, or chemotherapy.

In children and adolescents, problems other than solid tumors are much more likely to be the cause of pelvic pain. However, it is important even in this population to properly evaluate a complaint of pelvic pain, as malignant pelvic masses can sometimes occur.

Patient Assessment

Even an experienced clinician may find it challenging to accurately assess pain in a patient with cancer. Complete history and physical examination, including a thorough neurologic examination, are essential to localize the underlying pathology, identify the need for diagnostic tests, and choose therapeutic interventions correctly. The importance of obtaining a detailed understanding of the pelvic lesion(s) and elucidating the relationship of pathology to symptoms (clinicopathologic correlation) cannot be overemphasized. In a review of cancer pain consultations performed by a neurology-based pain service, the comprehensive evaluation of pain led to an identification of new malignant involvement in 65% of cases.[1]

In taking the patient’s history, focus on features that help identify the types of pain. Bone pain may be continuous at rest and markedly aggravated by body movements (incident pain). Sacral disease often causes midline pain radiating to the buttocks, which is made worse with sitting. Non-radicular referred pain may be associated with vague paresthesias and tenderness at the painful site. Radicular pain, in particular, may be paroxysmal, spontaneous, or provoked by movement or sensory stimulation. Straight leg raising implies dural traction.

It is important to understand pain in the context of other non-pain symptoms (eg, anxiety, mood, sleep) and suffering.

On physical examination, the practitioner may appreciate tenderness of the bony pelvis on palpation or percussion. Specific areas of sacral or coccygeal tenderness may be identified by external palpation, or by rectal or pelvic examination. Urinary retention may be demonstrated by bladder percussion. Laxity of the anal sphincter may be apparent on digital rectal examination.

Include the neurologic examination. Upper motor neuron dysfunction, if evidenced by increased tone and hyper-reflexia, should raise suspicion of spinal cord involvement. Findings of lower motor neuron weakness, indicating pelvic nerve involvement, may be accompanied by flaccidity, atrophy, muscle fasciculations, and hyporeflexia. Loss of bulbocavernosus and anal reflexes may also be present. Sensory examination should include the lower extremities, buttocks, external genitals, and the saddle area (to identify lesions of the sacral plexus).[2]

Because the correct interpretation of symptomatic and asymptomatic lesions on diagnostic imaging studies requires a thorough knowledge of the patient’s clinical presentation, it is strongly recommended that clinicoradiographic correlation be made by the examining physician.

Treatment

Neuropathic pain may be improved with treatment of the underlying cancer. There is some evidence that mitogen-activated protein kinase (MAPK)-signalling is an important factor driving neuropathic pain in neurons and/or glial cells. Anti-neoplastic agents that affect this pathway may alleviate cancer-related neuropathic pain directly and indirectly.[3]

Tumor bulk reduction should be a priority whenever possible. Many factors affect the choice of surgical technique, including tumor location, tumor extent, and general debility. Surgery may be indicated primarily for pain control.[4]

When cancer patients on opioid therapy require surgery, experts in pain medicine should participate in their care to assure smooth transitions between settings. Patients require reassurance that their preoperative opioid therapy does not preclude adequate perioperative and postoperative pain control.

Patients with radiosensitive tumors will benefit from consultation with a radiation oncologist, who will determineoptimal timing of radiation therapy in relation to surgery and chemotherapy treatments. External beam radiotherapy, intraoperative electron beam radiotherapy, and brachytherapy are options for the treatment of pelvic tumors. Stereotactic body radiotherapy is a promising new application. Radionuclides and bisphosphonates also play a role.

Corticosteroids may be used to reduce tumor-induced inflammation of nerves, afford pain relief, and positively affect neurologic outcome. The non-steroidal anti-inflammatory medications are also useful to control tumor-related inflammation of nerves and nociceptive nerve pain.

In recent years, guidelines have been published for the use of opioid analgesics and adjuvant analgesics for neuropathic pain.[5-8] Opioids are effective and usually are required to manage persistent severe neuropathic pain. Adjuvant medications including antidepressants (tricyclics, serotonin-
norepinephrine reuptake inhibitors [SNRIs]) and anti-
convulsants (gabapentin, pregabalin) are combined for relief of deafferentation neuropathic pain. When multiple psychoactive medications including opioids are used in a complex pharmacotherapy regimen, careful stepwise titration is indicated with close monitoring for side effects, particularly sedation and cognitive dysfunction. Topical lidocaine is useful at the painful sites, and patches can be applied on the spine as a type of pain block. Topical capsaicin may also be used. For refractory neuropathic pain, implanted intrathecal pumps may be considered for the addition of some medications that cannot be given systemically.

Neuroablative procedures can be considered when the benefit-to-risk ratio favors analgesia over the potential for further neurologic compromise. Destruction of the nervous tissue may be accomplished by anesthetic or surgical means. Chemical epidural or intrathecal neurolysis may be chosen to effect single or multiple nerve root interruption; both approaches entail the risk of acute neurologic deterioration, which may be irreversible.[9] The midline myelotomy may be indicated in patients with severe midline sacral pain and bladder or bowel compromise resulting from tumor of the sacrum.

Key Points in Dr. Weinstein’s Approach to Neuropathic Pain Caused by Pelvic Masses

Physical medicine and rehabilitation range from active programs to supportive and palliative care. The goals of rehabilitation often include relieving pain, improving ambulation, achieving weight-bearing and transfers, protecting the skin, and restoring bladder and bowel function. Painful sexual dysfunction, due in part to damaged nerves, is a frequent complication of pelvic cancer and its treatment in patients of both sexes, and should be addressed. The potential for the recovery of function in cases of pelvic tumor and neuropathic pain varies by tumor type, the nature and degree of neurologic involvement, the oncologic status, and the patient’s general medical condition. Long-term survivors should be encouraged to continue with physical programs to maximize their functional recovery.

Comprehensive care of the patient with severe neuropathic pain and advanced disease is essential. For patients with less than 6 months’ life expectancy, emotional and spiritual support for patient and family is needed for anticipatory grieving. Palliative care and hospice teams will provide essential services during this time.

Conclusion

Pain control for patients with pelvic neoplasm and neuropathic pain should remain a high priority regardless of prognosis. Clinicians are encouraged to work in a coordinated interdisciplinary fashion to carefully select those interventions that will achieve therapeutic goals for the individual patient and his or her family.

Disclosures:

The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Gonzales GR, Elliott KJ, Portenoy RK, et al. The impact of a comprehensive evaluation in the management of cancer pain. Pain. 1991;47:141.

2. Haanpää M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain. 2011;152:14-27.

3. Kersten C, Cameron MG. Cetuximab alleviates neuropathic pain despite tumour progression. BMJ Case Rep. 2012 Jun 14. doi:10.1136/bcr.12.2011.5374.

4. Quraishi NA, Giannoulis KE, Manoharan SR, et al. Surgical treatment of cauda equina compression as a result of metastatic tumours of the lumbo-sacral junction and sacrum. Eur Spine J. 2013;22(suppl 1):S33-7.

5. Piano V, Verhagen S, Schalkwijk A, et al. Treatment for neuropathic pain in patients with cancer: comparative analysis of recommendations in national clinical practice guidelines from European countries. Pain Pract. 2013 Jan 30. [Epub ahead of print]

6. Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010;85(suppl 3):S3-14.

7. Attal N, Cruccu G, Baron R, et al; European Federation of Neurological Societies. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17:1113-e88.

8. Backonja MM. Neuropathic pain therapy: from bench to bedside. Semin Neurol. 2012;32:264-8.

9. Birthi P, Sloan P. Interventional treatment of refractory cancer pain. Cancer J. 2013;19:390-6.