Myoclonus Patients receiving very high doses of opioids for

9.4.7.8 Urinary Retention Urinary retention can be caused by any opioid but

is seen more frequently with epidural or spinal opioids, often after rapid dose escalation. Interventions to help treat urinary retention include external bladder pressure, intermittent catheteriza- tion, and bethanechol or tamsulosin to stimulate bladder contraction. However, the easiest and least invasive way to manage this is through opioid rota- tion. Gallo et al. 2008 have shown in adult post- operative patients treated with morphine PCA that low- dose naloxone improved urinary residuals and increased urinary frequency.

9.5 Neuropathic Pain

Neuropathic pain, as described in Sect. 9.3 , is caused by damage to nociceptors and nociceptive pathways leading to abnormal pain signaling. Neuropathic pain has not been well studied in children. Characteristics that make neuropathic pain distressful include underassessment, pro- longed duration and poor response to currently available treatments Simon et al. 2012 . Causes of neuropathic pain include lesions of the spinal cord, tumor-related pain that may damage tissues and nerves, and chemotherapeutic agents such as vincristine see Sect. 9.8.1 , cisplatin, and pacli- taxel. Symptoms can last for months to years and can be exacerbated at the end of life Drake et al. 2003 . Guidelines on assessment and diagnostic scales for evaluation have been designed for adults and can be used in adolescents Haanpaa et al. 2011 . Diagnosis in children is based primarily on symp- tom character and quality see Sects. 9.3 and 9.8.1 . A Cochrane review in adults found mixed results for the use of opioids in the treatment of neuropathic pain Eisenberg et al. 2006 . Adjuvants are typically used with opioids since an effective pain response with opioids alone may not be achieved Chaparro et al. 2012 . Adjuvant medica- tions can cause signifi cant side effects requiring patient and family education about these effects. Systematic evidence on the use of such adjuvant agents in pediatric oncology patients is lacking Jacob 2004 ; Anghelescu et al. 2014 . Additionally, these medications can be used solely but require weeks of gradual titration. Topical agents such as capsaicin and lidocaine have shown some promise in producing analgesia in adult populations Babbar et al. 2009 ; Cheville et al. 2009 .

9.5.1 Calcium Channel Blockers

Calcium channel blockers such as gabapentin and pregabalin bind presynaptic voltage-gated calcium channels in the dorsal horn reducing the release of neuroexcitatory transmitters such as glutamate, noradrenaline and substance P. These agents have been the most studied in the pedi- atric population for neuropathic pain and inhibit the development of hyperalgesia and allodynia Buck 2002 ; Vondracek et al. 2009 . Doses can be titrated upwards as often as every 3 days although side effects may be limiting see Sect. 9.8.1 for dosing. Side effects include lethargy, nausea and vomiting, dizziness, weight gain, and behavioral problems such as aggression, restlessness, and hyperactivity. Gabapentin and pregabalin are renally excreted and doses must be adjusted for renal insuffi ciency or failure.

9.5.2 Serotonin and Norepinephrine

Reuptake Inhibitors SNRIs inhibit serotonin and norepinephrine reuptake and have no effect on postsynaptic receptors. A few adult studies have shown improved neuropathic pain and minimal side effects with these agents Goodyear-Smith and Halliwell 2009 . Nausea is the most common reported side effect. Doses are generally titrated upwards on a weekly basis. Venlafaxine is avail- able in an extended release form.

9.5.3 Tricyclic Antidepressants

The mechanism of action of tricyclic antidepres- sants TCAs is not well understood but appears to result from a combination of serotonin and nor- epinephrine presynaptic reuptake and inhibition 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