CHAPTER 78: Muscle Relaxants and α₂ Agonists for Pain Management

INTRODUCTION

Skeletal muscle relaxants are frequently used in patients with both acute and chronic pain when a component of muscle spasm is thought to be contributing to pain symptomatology. They are also used in the management of disorders in which spasticity is a prominent feature, such as multiple sclerosis, cerebral palsy, and after spinal cord injury or stroke with paresis. A wide variety of muscle relaxants are available, and selection of an agent for use may be influenced by factors such as cost, perceived potency, side effect profile, chronicity of pain, and addictive potential (or lack thereof). Commonly used muscle relaxants in the United States include baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, diazepam, metaxalone, methocarbamol, orphenadrine, and tizanidine.

The α₂ agonists are well known historically for their use in the management of hypertension, but more recently, these agents have been found effective in a variety of pain management, anesthesia, and critical care applications. These applications include use in perioperative sedation and as adjuncts to regional and neuraxial anesthesia for pain management, including the treatment of refractory cancer pain. α₂ Agonists have also been used in the palliative care setting to reduce pain and the distress of the dying and to facilitate withdrawal of ventilatory support. Additionally, they may be useful in the management of opioid-induced hyperalgesia and opioid and nicotine withdrawal. α₂ Agonists currently in clinical use include clonidine, tizanidine, and dexmedetomidine.

MUSCLE RELAXANTS

Muscle relaxants are most often used in the management of acute musculoskeletal pain but are also commonly combined with other analgesic agents in some chronic pain management regimens. These agents should be distinguished from the nondepolarizing and depolarizing muscle relaxants that are used to provide paralysis of skeletal and respiratory muscles during general anesthesia and act by production of blockade of neuromuscular conduction. The mechanism of action of the “muscle relaxant” agents used for managing muscle spasm is not fully understood, but in general, most of these drugs act centrally by suppressing polysynaptic reflexes in the spinal cord and via depressant effects on the central nervous system (CNS). This section describes the pharmacologic profile of the currently available skeletal muscle relaxants.

BACLOFEN

Baclofen is marketed in the United States under the brand name Lioresal. It is labeled for use in the management of disorders in which spasticity is present, such as multiple sclerosis and spinal cord injury. Unlabeled indications for the use of baclofen include intractable hiccups and trigeminal neuralgia and for the relief of intractable pain.¹ Baclofen is available for oral and intrathecal use. Baclofen is thought to act by inhibition of monosynaptic and polysynaptic reflex transmission at the level of the spinal cord, possibly through hyperpolarization of primary afferent nerve terminals.¹ It is derived from γ-aminobutyric acid (GABA), an inhibitory neurotransmitter thought to play an important role in pain transmission.² This may ...