Cancer Pain and Co-Analgesics

Cancer Pain and Co-Analgesics

1. The problem of cancer pain — definition, epidemiology, and pathophysiological framing

• Cancer pain is a multi-mechanistic pain syndrome; clinical cancer pain syndromes "typically represent a combination of ... inflammatory and neuropathic mechanisms" rather than a single pain type (G&G 14e Ch.23, p.450).
• Failure to adequately manage pain has measurable adverse physiological consequences: autonomic hyperreactivity (↑ blood pressure, ↑ heart rate, suppressed GI motility, reduced secretions), reduced mobility (deconditioning, muscle wasting, joint stiffening, decalcification), and deleterious psychological changes (depression, helplessness, anxiety) (G&G 14e Ch.23, p.466).
• Pain is now treated as the "fifth vital sign"; adequate pain assessment and management are standard of care by many accrediting bodies and by law in many jurisdictions (G&G 14e Ch.23, p.466).
• Nociceptive (inflammatory) pain arises from tissue injury/inflammation with peripheral terminal sensitisation; neuropathic pain arises from nerve injury with ectopic activity from neuromas and dorsal root ganglia, spinal (central) sensitisation, glial activation, and loss of constitutive inhibitory circuits such that low-threshold Aβ input evokes pain (allodynia) (G&G 14e Ch.23, p.450).
  • Cancer-relevant neuropathic mechanisms include chemotherapy-induced polyneuropathy and tumour-related nerve compression/infiltration; post-herpetic and diabetic polyneuropathy are analogous models (G&G 14e Ch.23, p.450).
• Two dimensions of the pain experience are pharmacologically distinct: the sensory-discriminative dimension (intensity) and the affective-motivational dimension (suffering); opioids act on both, and even sub-analgesic morphine doses can blunt the affective response before the perceived intensity (G&G 14e Ch.23, pp.450–451).
• Clinical corollary for cancer pain: continuous dull pain (tissue injury/inflammation) is relieved more effectively by opioids than sharp intermittent pain; neuropathic pain responds less well to opioids and requires higher doses — the pharmacological rationale for co-analgesics (G&G 14e Ch.23, pp.450, 451).