Fundamental sex differences in morphine withdrawal-induced neuronal plasticity.

Withdrawal from systemic opioids can induce long-term potentiation (LTP) at spinal C-fibre synapses ("opioid-withdrawal-LTP"). This is considered to be a cellular mechanism underlying opioid withdrawal-induced hyperalgesia, which is a major symptom of the opioid withdrawal syndrome. Opioids can activate glial cells leading to the release of proinflammatory mediators.

Withdrawal from an opioid induces a transferable memory trace in the cerebrospinal fluid.

Opioids are the most powerful analgesics available to date. However, they may also induce adverse effects including paradoxical opioid-induced hyperalgesia. A mechanism that might underlie opioid-induced hyperalgesia is the amplification of synaptic strength at spinal C-fibre synapses after withdrawal from systemic opioids such as remifentanil ("opioid-withdrawal long-term potentiation [LTP]").

VGluT3⁺ primary afferents play distinct roles in mechanical and cold hypersensitivity depending on pain etiology.

Sensory nerve fibers differ not only with respect to their sensory modalities and conduction velocities, but also in their relative roles for pain hypersensitivity. It is presently largely unknown which types of sensory afferents contribute to various forms of neuropathic and inflammatory pain hypersensitivity. Vesicular glutamate transporter 3-positive (VGluT3(+)) primary afferents, for example, have been implicated in mechanical hypersensitivity after inflammation, but their role in neuropathic pain remains under debate.