Tricyclic Antidepressants Neuropathic Pain

of sodium channels. TCAs used in management of neuropathic pain include amitriptyline, imip- ramine, doxepin, desipramine and nortriptyline. Amitriptyline, imipramine, and doxepin are ter- tiary amines and cause increased levels of seda- tion. Other side effects include anticholinergic effects such as urinary retention, dry mouth, con- stipation and blurred vision. Doses should be titrated upwards weekly. TCAs are contraindi- cated in epileptic children because they lower the seizure threshold and in children with heart fail- ure or cardiac conduction defects due to QTc pro- longation effects.

9.6 Non-pharmacologic

Treatment of Pain The combination of pharmacologic and non- pharmacologic techniques to relieve pain and improve comfort has become increasingly recog- nized as complementary components in pain management Twycross et al. 2009 . Non- pharmacologic treatments address both physical and psychological aspects of pain and are often combined for improved pain control Culbert and Olness 2010 . Children with cancer often use alternative therapies in conjunction with standard pharmacologic treatments Friedman et al. 1997 . It is important to create a treatment plan that combines non-pharmacologic modalities that engage the child and compliment the child’s energy level and comorbidities. Early introduc- tion of these techniques helps them become ther- apeutically effective over time. Ideally all patients would utilize complementary therapies, espe- cially when faced with chronic pain, although this is often limited by lack of resources.

9.6.1 Guided Imagery

Guided imagery uses personalized storytelling to aid children in mastering situations that provoke anxiety or fear. Parental involvement in the process is encouraged so the story can be retold during stressful treatments or procedures. Attention- distraction imagery involves teaching children to imagine a pleasant mental image during a painful experience Turk 1978 . Several studies have dem- onstrated the synergy of guided imagery with phar- macologic therapy in reducing pain and distress Kuttner et al. 1988 . In children undergoing bone marrow aspiration, an 18 reduction in behavioral distress scores and 25 reduction in self-reported pain scores has been noted with guided imagery Jay et al. 1987 . Imagery has been studied in older children and adults but has been particularly help- ful in children from the age of 3–6 years where the boundaries between fantasy and reality are less concrete Kuttner et al. 1988 ; Syrjala et al. 1995 .

9.6.2 Biofeedback

Biofeedback is the process of converting physio- logic signals such as blood pressure, pulse, mus- cle contractions, skin temperature and sweat response into audio or visual signals. Children are taught to observe these signals to help volun- tarily control their physiologic response to pain and stress. Biofeedback is commonly used by pediatric anesthesia services for pain and anxiety management Lin et al. 2005 . Most studies dem- onstrating success using biofeedback have been conducted in children with chronic headache, with a 50 symptom reduction in 23 of chil- dren Blanchard and Schwarz 1988 ; Hermann and Blanchard 2002 .

9.6.3 Acupuncture

Acupuncture is an ancient Chinese healing tradi- tion that inserts needles into acupuncture points to balance the body’s energy. Older children are more likely to prefer acupuncture as a comple- mentary technique to manage pain Tsao 2006 . Acupuncture has been shown effective in postop- erative and chronic pain, reducing cancer-related pain by 36 at 2 months from baseline Alimi et al. 2003 . An adult study of acupuncture and chemotherapy-induced nausea and vomiting showed that over a 5 day period, a median of ten less episodes of nausea and vomiting were reported per patient in those who received acupuncture with pharmacologic therapy versus pharmacologic ther- apy alone Shen et al. 2000 .

9.6.4 Transcutaneous Electrical

Nerve Stimulation Transcutaneous electrical nerve stimulation TENS units provide electrical stimulation via electrodes to the underlying nerves near the source of maximal pain. A Cochrane review found confl icting evidence on the effi cacy of TENS units in alleviating chronic low-back pain in adults Khadilkar et al. 2008 . Small pediatric studies have showed moderate success using TENS for chronic back pain in children Van Epps et al. 2007 . No studies in pediatric oncol- ogy patients have been reported.

9.6.5 Other Complementary

Therapies Several studies conducted in adults have demon- strated effi cacy of other complementary therapies such as music therapy, support groups, and reiki in reducing the burden of pain and anxiety. Music therapy has been shown to increase length of life in adult hospice nursing home patients Hilliard 2004 . A 1-year prospective, randomized study demonstrated the value of support groups in reducing mood-disturbance scores, decreasing phobia and improving maladaptive responses in women with metastatic breast cancer Spiegel et al. 1981 . The use of reiki, a complementary technique using therapeutic touch, has shown improvement in quality of life rating and visual analogue scale pain rating for patients with can- cer Olson et al. 2003 .

9.7 Interventional Techniques

Anesthesiologists with expertise in pain manage- ment can aid in the treatment of refractory recal- citrant pain through interventional techniques including epidural or intrathecal injections and peripheral nerve blocks. These techniques are used when there are limiting side effects of opi- oids, neuropathic pain that is unresponsive to rapid escalation or massive doses of opioids, and with procedural anesthesia Collins et al. 1996 b . At the end of life, rapid escalation of opioid med- ications is often required Hewitt et al. 2008 . Central neuraxial blocks i.e., intrathecal or epi- dural blocks and continuous peripheral nerve blocks help avoid systemic toxicity when rapid escalation of oral medications is required. Relative contraindications to central neuraxial blocks include fever, thrombocytopenia, wound at the catheter site, vertebral or spinal metastases, or fractures at the catheter site. Pain blockade via these methods has demonstrated effi cacious anal- gesia with a moderation of opioid requirements and few side effects despite relative contraindica- tions to catheter placement Anghelescu et al. 2010 .

9.8 Oncology-Specifi c Pain

Issues

9.8.1 Vincristine-Related Peripheral

Neuropathy Vincristine is an effective antineoplastic agent used widely in pediatric oncology but is associ- ated with both autonomic and sensorimotor neu- ropathy leading to peripheral neuropathy and neuropathic pain Moore 2009 . Symptoms of neuropathic pain due to vincristine include tin- gling, shooting pain, numbness, and pins-and- needles- type pain primarily in the hands, feet, and legs. Vincristine disrupts microtubular for- mation during mitosis and damages intraepider- mal nerve fi bers possibly via mitochondrial dysfunction. Longer axons tend to be most vul- nerable, thus explaining the stocking glove distri- bution pattern of the neuropathy Han and Smith 2013 . Vincristine toxicity is signifi cant and can lead to dose reduction and delays in therapy. In patients being treated for acute lymphoblastic leukemia ALL, 35 experienced at least one episode of neuropathic pain, with events clus- tered around periods of weekly vincristine administration Anghelescu et al. 2011 .