Table 1

The current state of knowledge on mechanisms of analgesia in fascial plane blocks

What is known	What is uncertain
Nerves run in and through fascial planes. LA spreads in fascial planes and can achieve sufficiently high concentrations for neural conduction blockade. LA can spread out of fascial planes into adjacent tissue compartments. Neural conduction block requires only relatively small amounts of LA. Different nerve fiber types have different sensitivities to LA. Clinically significant blockade of nociceptive transmission can be achieved without complete sensory or motor blockade. FPBs do not always result in expected patterns of cutaneous sensory blockade. Pain from surgery or trauma originates from cutaneous tissues and deeper tissues, including muscle, connective tissue, and bone. FPBs produce peak plasma lidocaine concentrations in the range associated with therapeutic intravenous lidocaine infusion. Bupivacaine, ropivacaine, and lidocaine have broadly similar mechanisms of action and receptor interactions.	The degree to which cadaveric studies of injectate spread correspond to injectate spread and clinical effect in living human subjects. Determinants of LA spread within and beyond fascial planes in individual patients. Determinants of vascular absorption and LA plasma concentration in individual patients. The exact influence of volume, concentration and mass of LA on clinical efficacy of FPBs. The extent to which FPBs block nociception from deeper musculoskeletal tissues. The contribution of motor nerve blockade to analgesia in certain pain syndromes. If equipotent doses of intravenous bupivacaine and ropivacaine have similar systemic analgesic effects to intravenous lidocaine. If the plasma concentrations of bupivacaine and ropivacaine resulting from FPBs are sufficient to produce clinically significant systemic analgesia. The molecular mechanisms of LA action that are directly relevant to the clinical analgesia associated with FPBs and different pain syndromes. The relative contribution of localized and systemic effects of LA to clinical analgesia in FPBs. If LA additives in FPBs consistently improve clinical analgesia and whether this is primarily mediated by a local or systemic effect.

What is known

What is uncertain

Nerves run in and through fascial planes.
LA spreads in fascial planes and can achieve sufficiently high concentrations for neural conduction blockade.
LA can spread out of fascial planes into adjacent tissue compartments.
Neural conduction block requires only relatively small amounts of LA.
Different nerve fiber types have different sensitivities to LA.
Clinically significant blockade of nociceptive transmission can be achieved without complete sensory or motor blockade.
FPBs do not always result in expected patterns of cutaneous sensory blockade.
Pain from surgery or trauma originates from cutaneous tissues and deeper tissues, including muscle, connective tissue, and bone.
FPBs produce peak plasma lidocaine concentrations in the range associated with therapeutic intravenous lidocaine infusion.
Bupivacaine, ropivacaine, and lidocaine have broadly similar mechanisms of action and receptor interactions.

The degree to which cadaveric studies of injectate spread correspond to injectate spread and clinical effect in living human subjects.
Determinants of LA spread within and beyond fascial planes in individual patients.
Determinants of vascular absorption and LA plasma concentration in individual patients.
The exact influence of volume, concentration and mass of LA on clinical efficacy of FPBs.
The extent to which FPBs block nociception from deeper musculoskeletal tissues.
The contribution of motor nerve blockade to analgesia in certain pain syndromes.
If equipotent doses of intravenous bupivacaine and ropivacaine have similar systemic analgesic effects to intravenous lidocaine.
If the plasma concentrations of bupivacaine and ropivacaine resulting from FPBs are sufficient to produce clinically significant systemic analgesia.
The molecular mechanisms of LA action that are directly relevant to the clinical analgesia associated with FPBs and different pain syndromes.
The relative contribution of localized and systemic effects of LA to clinical analgesia in FPBs.
If LA additives in FPBs consistently improve clinical analgesia and whether this is primarily mediated by a local or systemic effect.

FPB, fascial plane block; LA, local anesthetic.