Overview of opioids in pain management

Opioids achieve analgesia by reducing transmission of nociceptive impulses (through effects at central nervous system mu-receptors) and modulating the descending inhibitory pathways from the brain. Some opioids (eg tramadol, tapentadol) also produce analgesia via nonopioid receptors. See Overview of opioids commonly used in pain management for prescribing considerations.

Opioid use is generally limited to acute pain or cancer pain. It is difficult to define a cohort of patients with chronic noncancer pain that would consistently respond to opioids.

The role of opioids varies depending on the pain type. Opioids are often used for moderate or severe acute nociceptive pain (see Features of mild, moderate and severe acute pain for the features of moderate and severe pain). Opioids are ineffective for nociplastic pain, and are not consistently effective for neuropathic pain and should only be used under specialist advice. For further advice on the role of opioids in pain management, see:

Opioids can be administered via multiple routes; many factors influence the choice of administration route, see Routes of opioid administration for pain management.

In an opioid-naive patient, opioid doses are age-based. As people age, opioid dose requirements reduce because of increased brain sensitivity to opioid effects. Age-related physiological changes may also influence dose requirements (eg renal impairment, which may cause accumulation of active metabolites).

When prescribing opioids, potential harms must be considered alongside potential benefits. Harms include:

neuroadaptive and physiological changes (eg opioid tolerance, physical dependence, opioid-induced hyperalgesia)—may occur after 7 to 10 days of use
short- and long-term adverse effects
misuse, abuse and diversion, and poisoning.

Table 1. Neuroadaptive and physiological changes associated with opioid use
Change	Description	Clinical implications
opioid tolerance	decrease in drug effect over time the ability to induce tolerance differs between opioids	an increase in opioid dose may be required to achieve the same effect tolerance also develops to adverse effects (excluding constipation and miosis), but at different rates when opioid-tolerant patients are given opioids for acute pain they may be at increased risk of opioid-induced ventilatory impairment if additional doses rapidly and significantly exceed the patient’s usual baseline levels difficult to distinguish tolerance from opioid-induced hyperalgesia
physical dependence	abrupt opioid cessation, dose reduction or administration of a reversal agent will lead to a withdrawal syndrome; not the same as opioid-use disorder (addiction), but may be a component of it	if discontinuing short-term opioids (ie opioids used for less than 10 days), doses can be tapered quickly. This also applies when immediate-release opioids are prescribed for acute pain management in addition to a patient’s long-term opioid if discontinuing long-term opioids, gradually reduce the dose to minimise withdrawal symptoms [NB1]
opioid-induced hyperalgesia	increased sensitivity to pain, which may be diffuse and spread to locations other than the initial pain site mediated by opioid use rather than central sensitisation, but the underlying process is complex and not fully understood	increasing opioid doses does not improve pain and may worsen it consider opioid-induced hyperalgesia if a patient starts opioids for localised pain then develops total body pain improved pain relief following a dose reduction can confirm opioid-induced hyperalgesia. It is important to distinguish opioid-induced hyperalgesia from inadequate analgesia, in which a dose reduction will worsen pain
Note: NB1: Withdrawal symptoms include lacrimation; rhinorrhoea and sneezing; yawning; hot and cold flushes; sweating and piloerection; craving; anxiety; restlessness and irritability; disturbed sleep; gastrointestinal tract symptoms (eg anorexia, abdominal pain, nausea, vomiting, diarrhoea); muscle, bone and joint aches or pains; headache; muscle cramps; tremor.