Pruritus Pruritus is a common side effect of opioid use

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